RARE DISEASE
Chromomycosis
Chromomycosis
Chromomycosis
Synonyms: Chromoblastomycosis
Synonyms: Chromoblastomycosis
Synonyms: Chromoblastomycosis
Drug discovery
0
drugs
With orphan designations
Overview
Chromomycosis, also known as chromoblastomycosis, is a chronic subcutaneous fungal infection caused by dematiaceous fungi (e.g., Fonsecaea pedrosoi, Cladophialophora carrionii) following traumatic skin inoculation. It manifests as progressive verrucous nodules or plaques, predominantly on extremities, and can lead to severe limb deformity, secondary infections, or squamous cell carcinoma. Diagnosis relies on microscopy (muriform cells), culture, or molecular methods. Treatment includes systemic antifungals (itraconazole, terbinafine), adjunctive therapies (cryotherapy, surgery), and prolonged regimens to prevent recurrence [1][6][11].
Burden
Classified as a neglected tropical disease (NTD) with >7,700 reported cases globally, though underdiagnosis is widespread [2][4].
Average diagnostic delay: 9.2 years; high morbidity due to limb disability, social stigma, and rare malignant transformation [2][7][12].
Endemic in low-resource areas (e.g., Madagascar, Brazil); economic impact stems from lost productivity and limited healthcare access [4][7][12].
Therapies
First-line: Oral itraconazole (200 mg/day) or terbinafine (250 mg/day) for 6–12+ months [1][6].
Adjunctive options: Cryotherapy, photodynamic therapy, surgery (post-antifungal initiation), and topical 5-fluorouracil or imiquimod [1][3][18].
Refractory cases: Combination therapy (e.g., itraconazole + terbinafine) or experimental agents (e.g., acitretin) [8][18].
Categories: rare infectious diseases
Research Papers
473 drug discovery papers about Chromomycosis, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
473 drug discovery papers about Chromomycosis, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-06 | Simultaneous determination of imiquimod and terbinafine in skin permeation studies: Validation of a liquid chromatography method with fluorescence detection.
Chromoblastomycosis is a chronic, neglected subcutaneous mycosis posing significant therapeutic challenges. A topical strategy combining terbinafine (TBF), an antifungal, with imiquimod (IMQ), a TLR-7/8 agonist immunomodulator, has emerged a promising alternative. However, no validated analytical method is currently available to simultaneously quantify both drugs in skin, which is crucial for novel formulation development. This study reports the development and validation of a simple HPLC method with fluorescence detection (excitation 236 nm, emission 340 nm) for the simultaneous determination of TBF and IMQ extracted from porcine skin. Separation was achieved on a C8 reversed-phase column (125 × 4.0 mm, 5 μm) using a mobile phase of methanol and water (60,40, v/v), both containing 0.1% formic acid at a flow rate of 0.8 mL/min. The method showed excellent linearity (r > 0.999) over 0.01-1.0 μg/mL for IMQ and 0.1-2.0 μg/mL for TBF. Intra- and inter-day precision demonstrated coefficients of variation below 5%, and recovery rates from skin (79-105%) confirmed accuracy. Limits of detection were 0.001 μg/mL for IMQ and 0.004 μg/mL for TBF, with quantification limits of 0.02 μg/mL and 0.16 μg/mL, respectively. This selective, sensitive, and reproducible method represents a valuable analytical tool for supporting the development and quality control of topical formulations for chromoblastomycosis and other fungal skin diseases.
2026-07-29 | Impaired NLRP3 inflammasome activation by chitin underlies refractory chromoblastomycosis caused by Fonsecaea pedrosoi muriform cells.
Macrophage NLRP3 activation is crucial for antifungal immunity, yet its role in chromoblastomycosis-a chronic subcutaneous mycosis typically caused by Fonsecaea pedrosoi-remains unclear. Unlike prior self-resolving models using conidia and hyphae, clinical disease features muriform cells, a parasitic form resistant to macrophages and linked to chronicity. Notably, chitin, a weak NLRP3 agonist, accumulates on the surface of muriform cells. This study investigates whether chitin accumulation modulates NLRP3 activation and promotes fungal persistence. Human chromoblastomycosis lesions were analyzed by IHC (MPO, CD86, NLRP3) and RT-PCR for cytokine transcripts. WT and NLRP3-/- mice were footpad-inoculated with F. pedrosoi muriform cells for in vivo assessment. Flow cytometric bead array quantified IL-1β, IL-6, IL-10, TNF-α, and IL-17A in footpad homogenates, and the same panel (excluding IL-17A) in stimulated BMDM supernatants. NLRP3 pathway activation in BMDMs was confirmed by western blotting and immunofluorescence. In human lesions, marked MPO+ neutrophil recruitment encapsulated muriform cells, yet multinucleated giant cells sequestered some fungal elements from neutrophils. Despite robust NLRP3 expression and elevated IL-1β, IL-6, TNF-α, and IL-10 versus normal skin (all p < 0.01), muriform cells persisted in tissue. In WT mice, lesions transitioned from purulent (day 7) to granulomatous (day 90), concurrent with declining IL-1β, IL-17A, IL-6, and TNF-α. MPO+ neutrophils abundantly surrounded muriform cells at day 7; at day 90, F4/80+ macrophages enveloped most fungi without elimination, forming multinucleated giant cells-recapitulating human pathology. In NLRP3-/- mice, IL-1β and IL-17A were produced in an NLRP3-independent manner and showed no decline over time. Muriform cells progressively budded and transitioned to hyphae both inside and outside giant cells; MPO+ neutrophils preferentially localized to hyphal areas, while macrophages remained around muriform cells, suggesting compartmentalized inflammation. In vitro, chitinase-treated muriform cells induced higher NLRP3-dependent IL-1β, IL-6, TNF-α, and IL-10 in WT BMDMs versus intact cells (all p < 0.01). Mechanistically, chitin accumulation partially suppressed NF-κB phosphorylation, reducing NLRP3 expression, caspase-1 cleavage, and ASC speck formation. NLRP3 mediates host defense against muriform cells yet fails to resolve chronic infection. Chitin accumulation on muriform cells attenuates NLRP3 activation, thereby promoting chromoblastomycosis chronicity.
2026-07-24 | Chromoblastomycosis Leading to Squamous Cell Carcinoma: An Overlooked Outcome of a Neglected Tropical Disease.
Chromoblastomycosis is a neglected tropical skin disease acquired through traumatic inoculation of dematiaceous fungi. It is characterized clinically by a chronic granulomatous infection of the skin and subcutaneous tissue. Delays in diagnosis and limited access to antifungal therapy contribute to prolonged disease, recurrent inflammation, and debilitating sequelae. A rare but devastating complication is squamous cell carcinoma (SCC) associated with long-standing lesions, which may necessitate extensive surgery or amputation and can be fatal. In this review, we summarize reported epidemiology and clinical risk factors for SCC complicating chromoblastomycosis. We also discuss plausible inflammatory mechanisms of malignant transformation and propose pragmatic clinical and public health interventions, including decentralized microscopy-based diagnosis, timely antifungal access, and biopsy-triggered surveillance of chronically inflamed lesions, to reduce preventable morbidity.
2026-07-17 | AN UNUSUAL CASE OF CHROMOBLASTOMYCOSIS DUE TO FONSECAEA PEDROSOI IN SOUTH KERALA FOLLOWING A LEECH BITE: A CASE REPORT
Background: Chromoblastomycosis is a chronic cutaneous and subcutaneous fungal infection caused by melanized or brown-pigmented fungi, most commonly Fonsecaea pedrosoi. Purpose: This case report describes an unusual instance of chromoblastomycosis caused by F. pedrosoi in a woman from South Kerala with a preceding history of a leech bite, highlighting the importance of combining clinical examination, histopathology, fungal culture, and molecular sequencing for accurate diagnosis and effective management of this rare and chronic fungal infection. Case: A 54-year-old housewife presented with a 3 × 2 cm erythematous plaque on the dorsal aspect of left hand at the site of anatomical snuffbox. She reported a history of leech bite four years back at the same site. Dark pigmented colonies were isolated on Sabouraud dextrose agar. Skin biopsy for histological analysis, revealed sclerotic bodies, and Sanger sequencing. The patient was treated with oral itraconazole for two months. Result: The diagnosis of chromoblastomycosis was confirmed through fungal culture, histopathological examination revealing sclerotic bodies, and Sanger sequencing identifying F. pedrosoi. The patient responded well to two months of oral itraconazole over two months, with no recurrence of lesions noted on follow-up. Conclusion: Accurate identification of chromoblastomycosis is crucial due to its resistance to treatment and varied clinical manifestations, which often lead to misdiagnosis. However, combining systemic antifungal therapy with physical and surgical modalities has been shown to improve outcomes such an atypical mode of transmission underscores the need for heightened clinical awareness, especially in endemic areas or among patients with unusual environmental exposures.
2026-07-05 | Efficacy of Isotretinoin in Treating Fungal Infections: A Systematic Review.
Objective: This systematic review evaluates the effectiveness of oral isotretinoin, either as monotherapy or in combination with antifungal agents, in treating fungal skin infections. Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) standards were adhered to in drafting the systematic review. An extensive search was performed in the following databases covering the last decade from January 2015 to December 2024: PubMed, Scopus, Web of Science and Google Scholar. The selection of eligible studies adhered to the PICOS criteria (Population, Intervention, Comparator, Outcome and Study design). Due to substantial heterogeneity in study designs, interventions and outcome measures, a quantitative meta-analysis was not feasible and findings were synthesized narratively. Results: Two hundred forty-nine articles concerning the use of isotretinoin for fungal infections were identified. Titles and abstracts of 152 studies were evaluated, resulting in 54 studies deemed eligible for full-text evaluation. Finally, this review considered 16 studies evaluating isotretinoin regimens ranging from low-dose schedules (10–20 mg/day) to weight-based dosing up to 0.5 mg/kg/day. Four studies were on dermatophytosis, three on seborrhoeic dermatitis and two on pityriasis versicolor and tinea, with isolated reports on chromoblastomycosis and mycosis fungoides. The most consistent evidence of clinical benefit was observed in recurrent dermatophytosis and seborrhoeic dermatitis, especially when isotretinoin was used as an adjunct to the standard therapy. Out of the six studies evaluated using the ROBINS-I tool, three studies exhibited a low RoB and three other studies demonstrated a serious RoB. The RoB 2.0 tool revealed that all the assessed RCTs exhibited high RoB, except for one study that raised some concerns. Conclusion: Isotretinoin has potential in the adjuvant treatment of fungal infections especially recurrent dermatophytosis but is more of a supportive than a standalone therapy. Clinical relevance: Isotretinoin may be a promising adjunctive therapy, especially in recurrent dermatophytosis and should be further investigated as a way to improve treatment outcomes and reduce disease recurrence.
antibodies
2026-05-04 | Single-cell RNA sequencing unravels T cell exhaustion underlying the chronicity of chromoblastomycosis.
Chromoblastomycosis (CBM) is a chronic, neglected tropical fungal infection. Its immunopathogenesis, particularly the mechanism underlying its chronicity, remains poorly understood. We performed single-cell RNA sequencing (scRNA-seq) on lesional skin from a CBM patient, followed by comprehensive bioinformatics analyses. We then used multiplex immunofluorescence (mIF) to validate CD4+ T cell exhaustion in CBM patient lesions and the mouse model of Fonsecaea pedrosoi infection. We identified a significantly expanded population of exhausted CD4+ T cells within the patient's lesions, which exhibited high co-expression of inhibitory receptors (PD-1, TIM-3, LAG-3) and functional impairment. Trajectory inference suggested a differentiation path from naive towards exhaustion within the chronic inflammatory environment. Cell-cell communication analysis implicated monocytes/macrophages (MoMacs) as key drivers of this process via persistent antigen presentation and ligand-receptor interactions such as CTLA4-CD80/86 and LGALS9-CD44. The accumulation of exhausted CD4+ T cells was confirmed in human CBM lesions by multiplex immunofluorescence (mIF), and the progressive development of exhaustion was recapitulated in the mouse model of Fonsecaea pedrosoi infection. Our findings establish CD4+ T cell exhaustion as an important mechanism underlying the chronicity of chromoblastomycosis, revealing a new immunopathological perspective for this neglected disease.
2025-04-23 | Raw data of the images involved in this study.
Chromoblastomycosis (CBM), a chronic subcutaneous infection caused by black fungi such as Fonsecaea monophora (F. monophora), is characterized by a low cure rate, high recurrence rate, and prolonged treatment duration. Neutrophils, one of the most important innate immune cells, play complex roles in the prevention of fungal infections. This study investigated the function of neutrophils in host defense against F. monophora using a neutrophil-depleted mouse model and in vitro co-culture conditions. Fungal burden, histopathological changes, and cytokine profiles were compared between neutrophil-depleted mice and isotype control mice. Our findings demonstrated that neutrophil depletion in mice led to impaired fungal clearance, prolonged inflammation in F. monophora infected footpad tissues, highlighting the critical role of neutrophils in controlling F. monophora infection. Histopathological analysis revealed extensive inflammatory cell infiltration, especially macrophages, accompanied by elevated levels of pro-inflammatory cytokines such as IL-1β, CCL3, IL-6, and TNF-α. Besides, we observed that neutrophils play a key role in inhibiting the morphological transition of F. monophora from conidia to hyphae and sclerotic-like cells. Notably, the F. monophora morphology was also associated with the formation of neutrophil extracellular traps (NETs) in in vitro experiment. These findings underscore the importance of neutrophil-mediate immune responses in early fungal clearance and their ability to influence F.monophora morphological transition. The study provides novel insights into the immune mechanisms underlying CBM and highlights the potential therapeutic implications of targeting neutrophil-mediated responses in CBM infections.
2025-04-23 | Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis.
Chromoblastomycosis (CBM), a chronic subcutaneous infection caused by black fungi such as Fonsecaea monophora (F. monophora), is characterized by a low cure rate, high recurrence rate, and prolonged treatment duration. Neutrophils, one of the most important innate immune cells, play complex roles in the prevention of fungal infections. This study investigated the function of neutrophils in host defense against F. monophora using a neutrophil-depleted mouse model and in vitro co-culture conditions. Fungal burden, histopathological changes, and cytokine profiles were compared between neutrophil-depleted mice and isotype control mice. Our findings demonstrated that neutrophil depletion in mice led to impaired fungal clearance, prolonged inflammation in F. monophora infected footpad tissues, highlighting the critical role of neutrophils in controlling F. monophora infection. Histopathological analysis revealed extensive inflammatory cell infiltration, especially macrophages, accompanied by elevated levels of pro-inflammatory cytokines such as IL-1β, CCL3, IL-6, and TNF-α. Besides, we observed that neutrophils play a key role in inhibiting the morphological transition of F. monophora from conidia to hyphae and sclerotic-like cells. Notably, the F. monophora morphology was also associated with the formation of neutrophil extracellular traps (NETs) in in vitro experiment. These findings underscore the importance of neutrophil-mediate immune responses in early fungal clearance and their ability to influence F.monophora morphological transition. The study provides novel insights into the immune mechanisms underlying CBM and highlights the potential therapeutic implications of targeting neutrophil-mediated responses in CBM infections.
2014-05-30 | Characterization of Scedosporium apiospermum Glucosylceramides and Their Involvement in Fungal Development and Macrophage Functions
Scedosporium apiospermum is an emerging fungal pathogen that causes both localized and disseminated infections in immunocompromised patients. Glucosylceramides (CMH, GlcCer) are the main neutral glycosphingolipids expressed in fungal cells. In this study, glucosylceramides (GlcCer) were extracted and purified in several chromatographic steps. Using high-performance thin layer chromatography (HPTLC) and electrospray ionization mass spectrometry (ESI-MS), N-2′-hydroxyhexadecanoyl-1-β-D-glucopyranosyl-9-methyl-4,8-sphingadienine was identified as the main GlcCer in S. apiospermum. A monoclonal antibody (Mab) against this molecule was used for indirect immunofluorescence experiments, which revealed that this CMH is present on the surface of the mycelial and conidial forms of S. apiospermum. Treatment of S. apiospermum conidia with the Mab significantly reduced fungal growth. In addition, the Mab also enhanced the phagocytosis and killing of S. apiospermum by murine cells. In vitro assays were performed to evaluate the CMHs for their cytotoxic activities against the mammalian cell lines L.929 and RAW, and an inhibitory effect on cell proliferation was observed. Synergistic in vitro interactions were observed between the Mab against GlcCer and both amphotericin B (AmB) and itraconazole. Because Scedosporium species develop drug resistance, the number of available antifungal drugs is limited; our data indicate that combining immunotherapy with the available drugs might be a viable treatment option. These results suggest that in S. apiospermum, GlcCer are most likely cell wall components that are targeted by antifungal antibodies, which directly inhibit fungal development and enhance macrophage function; furthermore, these results suggest the combined use of monoclonal antibodies against GlcCer and antifungal drugs for antifungal immunotherapy.
2012-07-17 | Surface phosphatase in Rhinocladiella aquaspersa: biochemical properties and its involvement with adhesion.
Rhinocladiella aquaspersa is an etiologic agent of chromoblastomycosis, a subcutaneous chronic infectious disease. In the present work, we found that the three morphological forms of this fungus (conidia, mycelia and sclerotic bodies) expressed different levels of ecto-phosphatase activity. Our results demonstrated that surface conidial enzyme is an acid phosphatase, inhibited by sodium salts of molybdate, orthovanadate and fluoride and that the inhibition caused by orthovanadate and molybdate was irreversible. The conidial ecto-phosphatase efficiently released phosphate groups from different phosphorylated substrates, causing a higher rate of phosphate removal when p-nitrophenylphosphate was used as substrate. This ecto-enzyme of R. aquaspersa is modulated by Co(2 +) ions and inorganic phosphate (Pi). Accordingly, removal of Pi from the culture medium resulted in a marked (121-fold) increase of ecto-phosphatase activity. Surface phosphatase activity is apparently involved in fungal adhesive properties, since the attachment of R. aquaspersa to epithelial cells was reversed by the pre-treatment of the conidia with orthovanadate, molybdate and anti-phosphatase antibody. Corroborating this finding, conidia with greater ecto-phosphatase activity (grown in Pi-depleted medium) showed higher adherence to epithelial cells than fungi cultivated in the presence of Pi.
proteins
2026-07-08 | Immunoproteomics and reverse vaccinology identify a protective T-cell epitope from Fonsecaea pedrosoi for experimental chromoblastomycosis.
Chromoblastomycosis is a chronic neglected tropical mycosis caused predominantly by the melanized fungus Fonsecaea pedrosoi. Current treatments are prolonged and frequently ineffective, highlighting the need for new therapeutic strategies. Here, we applied an integrated immunoproteomic and reverse vaccinology approach to identify immunogenic antigens from F. pedrosoi and evaluate their vaccine potential. Fungal proteins were separated by two-dimensional electrophoresis and immunoreactive proteins were detected using sera from infected mice. Mass spectrometry identified several antigenic proteins, including enolase and previously uncharacterized hypothetical proteins. Computational epitope prediction revealed a peptide candidate (Hp11696; LGFMSAFKASKLIAI) with high predicted affinity for MHC class II molecules. Functional assays demonstrated that Hp11696 stimulated antigen-specific CD4+ T-cell proliferation in splenocytes derived from infected animals. Immunization with Hp11696 significantly reduced fungal burden in a murine model of chromoblastomycosis and induced cytokine responses characterized by increased IFN-γ and IL-10 production. Collectively, these findings demonstrate that immunoproteomics-guided antigen discovery can identify protective peptide epitopes from fungal pathogens. The Hp11696 peptide represents a promising candidate for the development of peptide-based vaccines targeting chromoblastomycosis.
2026-03-02 | Antifungal activity of the antimicrobial peptide RP557 against priority fungal pathogens.
Background. Natural host defence molecules, part of innate immunity and the first line of defence, are evolutionarily conserved. Some pharmaceutical properties undesirable for clinical use led to the rational design of synthetic molecules with constructed peptide arrangements, giving a novel therapeutic avenue. A prior publication showed synthetic peptide RP557 inhibition and killing of fluconazole-sensitive and resistant Candida species isolates, biofilm inhibition, no resistance induction, direct membrane action, negligible mammalian cell toxicity and topical efficacy in a rodent vaginal candidiasis model. These findings highlight the relevance of investigating RP557 activity against other fungal pathogens.Objective. We evaluated the antifungal spectrum of the RP557 against World Health Organization-listed priority fungal pathogens, including endemic and skin fungal pathogens, both alone and in combination with commercial antifungal drugs.Methods. The antifungal spectrum was evaluated by broth dilution vs. clinical isolates, and we present 76 MICs (mcg ml-1) performed according to M27 or M38 CLSI documents, 35 checkerboard interactions with antifungals and 10 minimum fungicidal determinations.Results. Overall impression is robust activity vs. chromoblastomycosis and mycetoma species, Cryptococcus neoformans and Trichophyton spp.; broad MIC ranges within most species, least activity vs. Mucorales and Aspergillus spp.; and some promising drug interactions vs. Sporothrix spp. and Candida auris.Conclusion. Additional efficacy data in vivo is needed. Topical therapy could give local concentrations exceeding MICs, and burn or trauma prophylaxis or treatments are attractive potential targets owing to RP557 panmicrobial properties.
2025-05-02 | IL-18 production is required for the generation of a Th1 response during experimental chromoblastomycosis.
Chromoblastomycosis is a chronic fungal infection characterized by the formation of granulomatous lesions in the skin and subcutaneous tissues that begins after inoculation trauma. The disease is more frequently observed in tropical countries such as Brazil. Important studies have been shown a predominantly cell-mediated immune response during chromoblastomycosis. Results from our laboratory showed that Th1 responses are essential to induce protection during chromoblastomycosis. IL-18 is primarily produced by macrophages and is known to induce the production of IFNγ, a cytokine associated with Th1 cell activation. Once produced, IL-18 acts to promote Th1 cell differentiation and activation. Th1 cells, in turn, secrete cytokines such as IFNγ, which are critical for the elimination of intracellular pathogens, including fungi. IFNγ enhances the fungicidal activity of macrophages, promotes the development of antifungal effector mechanisms, and contributes to the containment of fungal growth. Our results indicate that F. pedrosoi is sensed by the NLRP3 inflammasome, which induces caspase-1 activation and production of IL-18. Moreover, IL-18 plays a crucial role in activating Th1 cells and controlling fungal loads during chromoblastomycosis. Further research into the mechanisms underlying IL-18-mediated immunity may lead to the development of novel therapeutic approaches for the treatment of this chronic fungal infection.
2024-04-05 | IL-18 production is required for the generation of a Th1 response during chromoblastomycosis
Abstract Chromoblastomycosis is a chronic fungal infection characterized by the formation of granulomatous lesions in the skin and subcutaneous tissues that begins after inoculation trauma. The disease is more frequently observed in tropical countries such as Brazil. Important studies have been shown a predominantly cell-mediated immune response during chromoblastomycosis. Results from our laboratory showed that Th1 responses are essential to induce protection during chromoblastomycosis. IL-18 is primarily produced by macrophages and is known to induce the production of IFNγ, a cytokine associated with Th1 cell activation. Once produced, IL-18 acts to promote Th1 cell differentiation and activation. Th1 cells, in turn, secrete cytokines such as IFNγ, which are critical for the elimination of intracellular pathogens, including fungi. IFNγ enhances the fungicidal activity of macrophages, promotes the development of antifungal effector mechanisms, and contributes to the containment of fungal growth. Our results indicate that F. pedrosoi is sensed by the NLRP3 inflammasome, which induces caspase-1 activation and production of IL-18. Moreover, IL-18 plays a crucial role in activating Th1 cells and controlling fungal loads during chromoblastomycosis. Further research into the mechanisms underlying IL-18-mediated immunity may lead to the development of novel therapeutic approaches for the treatment of this chronic fungal infection.
2018-02-26 | Transformation of Fonsecaea pedrosoi into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-γ production
Fonsecaea pedrosoi (F. pedrosoi) is the most common agent of chromoblastomycosis. Transformation of this fungus from its saprophytic phase into pathogenic sclerotic cells in tissue is an essential link to the refractoriness of this infection. Experimental studies in murine models have shown that the absence of CD4+ T cells impairs host defense against F. pedrosoi infection. Clinical research has also suggested that a relatively low level of the Th1 cytokine INF-γ and inefficient T cell proliferation are simultaneously present in patients with severe chromoblastomycosis upon in vitro stimulation with ChromoAg, an antigen prepared from F. pedrosoi. In the present study, we show that in mice intraperitoneally infected with F. pedrosoi-spores, -hyphae or in vitro-induced sclerotic cells respectively, the transformation of this causative agent into sclerotic cells contributes to a compromised Th1 cytokine production in the earlier stage of infection with impaired generation of neutrophil reactive oxygen species (ROS) and pan-inhibition of Th1/Th2/Th17 cytokine production with disseminated infection in the later stage by using a CBA murine Th1/Th2/Th17 cytokine kit. In addition, we have further demonstrated that intraperitoneal administration of recombinant mouse IFN-γ (rmIFN-γ) effectively reduces the fungal load in the infected mouse spleen, and dampens the peritoneal dissemination of F. pedrosoi-sclerotic cells. Meanwhile, exogeneous rmIFN-γ contributes to the formation and maintenance of micro-abscess and restores the decrease in neutrophil ROS generation in the mouse spleen infected with F. pedrosoi-sclerotic cells. Of note, we have once again demonstrated that it is a chitin-like component, but not β-glucans or mannose moiety, that exclusively accumulates on the outer cell wall of F. pedrosoi-sclerotic cells which were induced in vitro or isolated from the spleens of intraperitoneally infected BALB/c mice. In addition, our results indicate that decreased accumulation of chitin on the surface of live F. pedrosoi-sclerotic cells after chitinase treatment can be self-compensated in a time-dependent manner. Importantly, we have for the first time demonstrated that exclusive accumulation of chitin on the transformed sclerotic cells of F. pedrosoi is involved in an impaired murine Th1 cytokine profile, therefore promoting the refractoriness of experimental murine chromoblastomycosis.
small molecules
2026-08-06 | Simultaneous determination of imiquimod and terbinafine in skin permeation studies: Validation of a liquid chromatography method with fluorescence detection.
Chromoblastomycosis is a chronic, neglected subcutaneous mycosis posing significant therapeutic challenges. A topical strategy combining terbinafine (TBF), an antifungal, with imiquimod (IMQ), a TLR-7/8 agonist immunomodulator, has emerged a promising alternative. However, no validated analytical method is currently available to simultaneously quantify both drugs in skin, which is crucial for novel formulation development. This study reports the development and validation of a simple HPLC method with fluorescence detection (excitation 236 nm, emission 340 nm) for the simultaneous determination of TBF and IMQ extracted from porcine skin. Separation was achieved on a C8 reversed-phase column (125 × 4.0 mm, 5 μm) using a mobile phase of methanol and water (60,40, v/v), both containing 0.1% formic acid at a flow rate of 0.8 mL/min. The method showed excellent linearity (r > 0.999) over 0.01-1.0 μg/mL for IMQ and 0.1-2.0 μg/mL for TBF. Intra- and inter-day precision demonstrated coefficients of variation below 5%, and recovery rates from skin (79-105%) confirmed accuracy. Limits of detection were 0.001 μg/mL for IMQ and 0.004 μg/mL for TBF, with quantification limits of 0.02 μg/mL and 0.16 μg/mL, respectively. This selective, sensitive, and reproducible method represents a valuable analytical tool for supporting the development and quality control of topical formulations for chromoblastomycosis and other fungal skin diseases.
2026-07-29 | Impaired NLRP3 inflammasome activation by chitin underlies refractory chromoblastomycosis caused by Fonsecaea pedrosoi muriform cells.
Macrophage NLRP3 activation is crucial for antifungal immunity, yet its role in chromoblastomycosis-a chronic subcutaneous mycosis typically caused by Fonsecaea pedrosoi-remains unclear. Unlike prior self-resolving models using conidia and hyphae, clinical disease features muriform cells, a parasitic form resistant to macrophages and linked to chronicity. Notably, chitin, a weak NLRP3 agonist, accumulates on the surface of muriform cells. This study investigates whether chitin accumulation modulates NLRP3 activation and promotes fungal persistence. Human chromoblastomycosis lesions were analyzed by IHC (MPO, CD86, NLRP3) and RT-PCR for cytokine transcripts. WT and NLRP3-/- mice were footpad-inoculated with F. pedrosoi muriform cells for in vivo assessment. Flow cytometric bead array quantified IL-1β, IL-6, IL-10, TNF-α, and IL-17A in footpad homogenates, and the same panel (excluding IL-17A) in stimulated BMDM supernatants. NLRP3 pathway activation in BMDMs was confirmed by western blotting and immunofluorescence. In human lesions, marked MPO+ neutrophil recruitment encapsulated muriform cells, yet multinucleated giant cells sequestered some fungal elements from neutrophils. Despite robust NLRP3 expression and elevated IL-1β, IL-6, TNF-α, and IL-10 versus normal skin (all p < 0.01), muriform cells persisted in tissue. In WT mice, lesions transitioned from purulent (day 7) to granulomatous (day 90), concurrent with declining IL-1β, IL-17A, IL-6, and TNF-α. MPO+ neutrophils abundantly surrounded muriform cells at day 7; at day 90, F4/80+ macrophages enveloped most fungi without elimination, forming multinucleated giant cells-recapitulating human pathology. In NLRP3-/- mice, IL-1β and IL-17A were produced in an NLRP3-independent manner and showed no decline over time. Muriform cells progressively budded and transitioned to hyphae both inside and outside giant cells; MPO+ neutrophils preferentially localized to hyphal areas, while macrophages remained around muriform cells, suggesting compartmentalized inflammation. In vitro, chitinase-treated muriform cells induced higher NLRP3-dependent IL-1β, IL-6, TNF-α, and IL-10 in WT BMDMs versus intact cells (all p < 0.01). Mechanistically, chitin accumulation partially suppressed NF-κB phosphorylation, reducing NLRP3 expression, caspase-1 cleavage, and ASC speck formation. NLRP3 mediates host defense against muriform cells yet fails to resolve chronic infection. Chitin accumulation on muriform cells attenuates NLRP3 activation, thereby promoting chromoblastomycosis chronicity.
2026-07-24 | Chromoblastomycosis Leading to Squamous Cell Carcinoma: An Overlooked Outcome of a Neglected Tropical Disease.
Chromoblastomycosis is a neglected tropical skin disease acquired through traumatic inoculation of dematiaceous fungi. It is characterized clinically by a chronic granulomatous infection of the skin and subcutaneous tissue. Delays in diagnosis and limited access to antifungal therapy contribute to prolonged disease, recurrent inflammation, and debilitating sequelae. A rare but devastating complication is squamous cell carcinoma (SCC) associated with long-standing lesions, which may necessitate extensive surgery or amputation and can be fatal. In this review, we summarize reported epidemiology and clinical risk factors for SCC complicating chromoblastomycosis. We also discuss plausible inflammatory mechanisms of malignant transformation and propose pragmatic clinical and public health interventions, including decentralized microscopy-based diagnosis, timely antifungal access, and biopsy-triggered surveillance of chronically inflamed lesions, to reduce preventable morbidity.
2026-07-17 | AN UNUSUAL CASE OF CHROMOBLASTOMYCOSIS DUE TO FONSECAEA PEDROSOI IN SOUTH KERALA FOLLOWING A LEECH BITE: A CASE REPORT
Background: Chromoblastomycosis is a chronic cutaneous and subcutaneous fungal infection caused by melanized or brown-pigmented fungi, most commonly Fonsecaea pedrosoi. Purpose: This case report describes an unusual instance of chromoblastomycosis caused by F. pedrosoi in a woman from South Kerala with a preceding history of a leech bite, highlighting the importance of combining clinical examination, histopathology, fungal culture, and molecular sequencing for accurate diagnosis and effective management of this rare and chronic fungal infection. Case: A 54-year-old housewife presented with a 3 × 2 cm erythematous plaque on the dorsal aspect of left hand at the site of anatomical snuffbox. She reported a history of leech bite four years back at the same site. Dark pigmented colonies were isolated on Sabouraud dextrose agar. Skin biopsy for histological analysis, revealed sclerotic bodies, and Sanger sequencing. The patient was treated with oral itraconazole for two months. Result: The diagnosis of chromoblastomycosis was confirmed through fungal culture, histopathological examination revealing sclerotic bodies, and Sanger sequencing identifying F. pedrosoi. The patient responded well to two months of oral itraconazole over two months, with no recurrence of lesions noted on follow-up. Conclusion: Accurate identification of chromoblastomycosis is crucial due to its resistance to treatment and varied clinical manifestations, which often lead to misdiagnosis. However, combining systemic antifungal therapy with physical and surgical modalities has been shown to improve outcomes such an atypical mode of transmission underscores the need for heightened clinical awareness, especially in endemic areas or among patients with unusual environmental exposures.
2026-07-05 | Efficacy of Isotretinoin in Treating Fungal Infections: A Systematic Review.
Objective: This systematic review evaluates the effectiveness of oral isotretinoin, either as monotherapy or in combination with antifungal agents, in treating fungal skin infections. Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) standards were adhered to in drafting the systematic review. An extensive search was performed in the following databases covering the last decade from January 2015 to December 2024: PubMed, Scopus, Web of Science and Google Scholar. The selection of eligible studies adhered to the PICOS criteria (Population, Intervention, Comparator, Outcome and Study design). Due to substantial heterogeneity in study designs, interventions and outcome measures, a quantitative meta-analysis was not feasible and findings were synthesized narratively. Results: Two hundred forty-nine articles concerning the use of isotretinoin for fungal infections were identified. Titles and abstracts of 152 studies were evaluated, resulting in 54 studies deemed eligible for full-text evaluation. Finally, this review considered 16 studies evaluating isotretinoin regimens ranging from low-dose schedules (10–20 mg/day) to weight-based dosing up to 0.5 mg/kg/day. Four studies were on dermatophytosis, three on seborrhoeic dermatitis and two on pityriasis versicolor and tinea, with isolated reports on chromoblastomycosis and mycosis fungoides. The most consistent evidence of clinical benefit was observed in recurrent dermatophytosis and seborrhoeic dermatitis, especially when isotretinoin was used as an adjunct to the standard therapy. Out of the six studies evaluated using the ROBINS-I tool, three studies exhibited a low RoB and three other studies demonstrated a serious RoB. The RoB 2.0 tool revealed that all the assessed RCTs exhibited high RoB, except for one study that raised some concerns. Conclusion: Isotretinoin has potential in the adjuvant treatment of fungal infections especially recurrent dermatophytosis but is more of a supportive than a standalone therapy. Clinical relevance: Isotretinoin may be a promising adjunctive therapy, especially in recurrent dermatophytosis and should be further investigated as a way to improve treatment outcomes and reduce disease recurrence.
antibodies
2026-05-04 | Single-cell RNA sequencing unravels T cell exhaustion underlying the chronicity of chromoblastomycosis.
Chromoblastomycosis (CBM) is a chronic, neglected tropical fungal infection. Its immunopathogenesis, particularly the mechanism underlying its chronicity, remains poorly understood. We performed single-cell RNA sequencing (scRNA-seq) on lesional skin from a CBM patient, followed by comprehensive bioinformatics analyses. We then used multiplex immunofluorescence (mIF) to validate CD4+ T cell exhaustion in CBM patient lesions and the mouse model of Fonsecaea pedrosoi infection. We identified a significantly expanded population of exhausted CD4+ T cells within the patient's lesions, which exhibited high co-expression of inhibitory receptors (PD-1, TIM-3, LAG-3) and functional impairment. Trajectory inference suggested a differentiation path from naive towards exhaustion within the chronic inflammatory environment. Cell-cell communication analysis implicated monocytes/macrophages (MoMacs) as key drivers of this process via persistent antigen presentation and ligand-receptor interactions such as CTLA4-CD80/86 and LGALS9-CD44. The accumulation of exhausted CD4+ T cells was confirmed in human CBM lesions by multiplex immunofluorescence (mIF), and the progressive development of exhaustion was recapitulated in the mouse model of Fonsecaea pedrosoi infection. Our findings establish CD4+ T cell exhaustion as an important mechanism underlying the chronicity of chromoblastomycosis, revealing a new immunopathological perspective for this neglected disease.
2025-04-23 | Raw data of the images involved in this study.
Chromoblastomycosis (CBM), a chronic subcutaneous infection caused by black fungi such as Fonsecaea monophora (F. monophora), is characterized by a low cure rate, high recurrence rate, and prolonged treatment duration. Neutrophils, one of the most important innate immune cells, play complex roles in the prevention of fungal infections. This study investigated the function of neutrophils in host defense against F. monophora using a neutrophil-depleted mouse model and in vitro co-culture conditions. Fungal burden, histopathological changes, and cytokine profiles were compared between neutrophil-depleted mice and isotype control mice. Our findings demonstrated that neutrophil depletion in mice led to impaired fungal clearance, prolonged inflammation in F. monophora infected footpad tissues, highlighting the critical role of neutrophils in controlling F. monophora infection. Histopathological analysis revealed extensive inflammatory cell infiltration, especially macrophages, accompanied by elevated levels of pro-inflammatory cytokines such as IL-1β, CCL3, IL-6, and TNF-α. Besides, we observed that neutrophils play a key role in inhibiting the morphological transition of F. monophora from conidia to hyphae and sclerotic-like cells. Notably, the F. monophora morphology was also associated with the formation of neutrophil extracellular traps (NETs) in in vitro experiment. These findings underscore the importance of neutrophil-mediate immune responses in early fungal clearance and their ability to influence F.monophora morphological transition. The study provides novel insights into the immune mechanisms underlying CBM and highlights the potential therapeutic implications of targeting neutrophil-mediated responses in CBM infections.
2025-04-23 | Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis.
Chromoblastomycosis (CBM), a chronic subcutaneous infection caused by black fungi such as Fonsecaea monophora (F. monophora), is characterized by a low cure rate, high recurrence rate, and prolonged treatment duration. Neutrophils, one of the most important innate immune cells, play complex roles in the prevention of fungal infections. This study investigated the function of neutrophils in host defense against F. monophora using a neutrophil-depleted mouse model and in vitro co-culture conditions. Fungal burden, histopathological changes, and cytokine profiles were compared between neutrophil-depleted mice and isotype control mice. Our findings demonstrated that neutrophil depletion in mice led to impaired fungal clearance, prolonged inflammation in F. monophora infected footpad tissues, highlighting the critical role of neutrophils in controlling F. monophora infection. Histopathological analysis revealed extensive inflammatory cell infiltration, especially macrophages, accompanied by elevated levels of pro-inflammatory cytokines such as IL-1β, CCL3, IL-6, and TNF-α. Besides, we observed that neutrophils play a key role in inhibiting the morphological transition of F. monophora from conidia to hyphae and sclerotic-like cells. Notably, the F. monophora morphology was also associated with the formation of neutrophil extracellular traps (NETs) in in vitro experiment. These findings underscore the importance of neutrophil-mediate immune responses in early fungal clearance and their ability to influence F.monophora morphological transition. The study provides novel insights into the immune mechanisms underlying CBM and highlights the potential therapeutic implications of targeting neutrophil-mediated responses in CBM infections.
2014-05-30 | Characterization of Scedosporium apiospermum Glucosylceramides and Their Involvement in Fungal Development and Macrophage Functions
Scedosporium apiospermum is an emerging fungal pathogen that causes both localized and disseminated infections in immunocompromised patients. Glucosylceramides (CMH, GlcCer) are the main neutral glycosphingolipids expressed in fungal cells. In this study, glucosylceramides (GlcCer) were extracted and purified in several chromatographic steps. Using high-performance thin layer chromatography (HPTLC) and electrospray ionization mass spectrometry (ESI-MS), N-2′-hydroxyhexadecanoyl-1-β-D-glucopyranosyl-9-methyl-4,8-sphingadienine was identified as the main GlcCer in S. apiospermum. A monoclonal antibody (Mab) against this molecule was used for indirect immunofluorescence experiments, which revealed that this CMH is present on the surface of the mycelial and conidial forms of S. apiospermum. Treatment of S. apiospermum conidia with the Mab significantly reduced fungal growth. In addition, the Mab also enhanced the phagocytosis and killing of S. apiospermum by murine cells. In vitro assays were performed to evaluate the CMHs for their cytotoxic activities against the mammalian cell lines L.929 and RAW, and an inhibitory effect on cell proliferation was observed. Synergistic in vitro interactions were observed between the Mab against GlcCer and both amphotericin B (AmB) and itraconazole. Because Scedosporium species develop drug resistance, the number of available antifungal drugs is limited; our data indicate that combining immunotherapy with the available drugs might be a viable treatment option. These results suggest that in S. apiospermum, GlcCer are most likely cell wall components that are targeted by antifungal antibodies, which directly inhibit fungal development and enhance macrophage function; furthermore, these results suggest the combined use of monoclonal antibodies against GlcCer and antifungal drugs for antifungal immunotherapy.
2012-07-17 | Surface phosphatase in Rhinocladiella aquaspersa: biochemical properties and its involvement with adhesion.
Rhinocladiella aquaspersa is an etiologic agent of chromoblastomycosis, a subcutaneous chronic infectious disease. In the present work, we found that the three morphological forms of this fungus (conidia, mycelia and sclerotic bodies) expressed different levels of ecto-phosphatase activity. Our results demonstrated that surface conidial enzyme is an acid phosphatase, inhibited by sodium salts of molybdate, orthovanadate and fluoride and that the inhibition caused by orthovanadate and molybdate was irreversible. The conidial ecto-phosphatase efficiently released phosphate groups from different phosphorylated substrates, causing a higher rate of phosphate removal when p-nitrophenylphosphate was used as substrate. This ecto-enzyme of R. aquaspersa is modulated by Co(2 +) ions and inorganic phosphate (Pi). Accordingly, removal of Pi from the culture medium resulted in a marked (121-fold) increase of ecto-phosphatase activity. Surface phosphatase activity is apparently involved in fungal adhesive properties, since the attachment of R. aquaspersa to epithelial cells was reversed by the pre-treatment of the conidia with orthovanadate, molybdate and anti-phosphatase antibody. Corroborating this finding, conidia with greater ecto-phosphatase activity (grown in Pi-depleted medium) showed higher adherence to epithelial cells than fungi cultivated in the presence of Pi.
proteins
2026-07-08 | Immunoproteomics and reverse vaccinology identify a protective T-cell epitope from Fonsecaea pedrosoi for experimental chromoblastomycosis.
Chromoblastomycosis is a chronic neglected tropical mycosis caused predominantly by the melanized fungus Fonsecaea pedrosoi. Current treatments are prolonged and frequently ineffective, highlighting the need for new therapeutic strategies. Here, we applied an integrated immunoproteomic and reverse vaccinology approach to identify immunogenic antigens from F. pedrosoi and evaluate their vaccine potential. Fungal proteins were separated by two-dimensional electrophoresis and immunoreactive proteins were detected using sera from infected mice. Mass spectrometry identified several antigenic proteins, including enolase and previously uncharacterized hypothetical proteins. Computational epitope prediction revealed a peptide candidate (Hp11696; LGFMSAFKASKLIAI) with high predicted affinity for MHC class II molecules. Functional assays demonstrated that Hp11696 stimulated antigen-specific CD4+ T-cell proliferation in splenocytes derived from infected animals. Immunization with Hp11696 significantly reduced fungal burden in a murine model of chromoblastomycosis and induced cytokine responses characterized by increased IFN-γ and IL-10 production. Collectively, these findings demonstrate that immunoproteomics-guided antigen discovery can identify protective peptide epitopes from fungal pathogens. The Hp11696 peptide represents a promising candidate for the development of peptide-based vaccines targeting chromoblastomycosis.
2026-03-02 | Antifungal activity of the antimicrobial peptide RP557 against priority fungal pathogens.
Background. Natural host defence molecules, part of innate immunity and the first line of defence, are evolutionarily conserved. Some pharmaceutical properties undesirable for clinical use led to the rational design of synthetic molecules with constructed peptide arrangements, giving a novel therapeutic avenue. A prior publication showed synthetic peptide RP557 inhibition and killing of fluconazole-sensitive and resistant Candida species isolates, biofilm inhibition, no resistance induction, direct membrane action, negligible mammalian cell toxicity and topical efficacy in a rodent vaginal candidiasis model. These findings highlight the relevance of investigating RP557 activity against other fungal pathogens.Objective. We evaluated the antifungal spectrum of the RP557 against World Health Organization-listed priority fungal pathogens, including endemic and skin fungal pathogens, both alone and in combination with commercial antifungal drugs.Methods. The antifungal spectrum was evaluated by broth dilution vs. clinical isolates, and we present 76 MICs (mcg ml-1) performed according to M27 or M38 CLSI documents, 35 checkerboard interactions with antifungals and 10 minimum fungicidal determinations.Results. Overall impression is robust activity vs. chromoblastomycosis and mycetoma species, Cryptococcus neoformans and Trichophyton spp.; broad MIC ranges within most species, least activity vs. Mucorales and Aspergillus spp.; and some promising drug interactions vs. Sporothrix spp. and Candida auris.Conclusion. Additional efficacy data in vivo is needed. Topical therapy could give local concentrations exceeding MICs, and burn or trauma prophylaxis or treatments are attractive potential targets owing to RP557 panmicrobial properties.
2025-05-02 | IL-18 production is required for the generation of a Th1 response during experimental chromoblastomycosis.
Chromoblastomycosis is a chronic fungal infection characterized by the formation of granulomatous lesions in the skin and subcutaneous tissues that begins after inoculation trauma. The disease is more frequently observed in tropical countries such as Brazil. Important studies have been shown a predominantly cell-mediated immune response during chromoblastomycosis. Results from our laboratory showed that Th1 responses are essential to induce protection during chromoblastomycosis. IL-18 is primarily produced by macrophages and is known to induce the production of IFNγ, a cytokine associated with Th1 cell activation. Once produced, IL-18 acts to promote Th1 cell differentiation and activation. Th1 cells, in turn, secrete cytokines such as IFNγ, which are critical for the elimination of intracellular pathogens, including fungi. IFNγ enhances the fungicidal activity of macrophages, promotes the development of antifungal effector mechanisms, and contributes to the containment of fungal growth. Our results indicate that F. pedrosoi is sensed by the NLRP3 inflammasome, which induces caspase-1 activation and production of IL-18. Moreover, IL-18 plays a crucial role in activating Th1 cells and controlling fungal loads during chromoblastomycosis. Further research into the mechanisms underlying IL-18-mediated immunity may lead to the development of novel therapeutic approaches for the treatment of this chronic fungal infection.
2024-04-05 | IL-18 production is required for the generation of a Th1 response during chromoblastomycosis
Abstract Chromoblastomycosis is a chronic fungal infection characterized by the formation of granulomatous lesions in the skin and subcutaneous tissues that begins after inoculation trauma. The disease is more frequently observed in tropical countries such as Brazil. Important studies have been shown a predominantly cell-mediated immune response during chromoblastomycosis. Results from our laboratory showed that Th1 responses are essential to induce protection during chromoblastomycosis. IL-18 is primarily produced by macrophages and is known to induce the production of IFNγ, a cytokine associated with Th1 cell activation. Once produced, IL-18 acts to promote Th1 cell differentiation and activation. Th1 cells, in turn, secrete cytokines such as IFNγ, which are critical for the elimination of intracellular pathogens, including fungi. IFNγ enhances the fungicidal activity of macrophages, promotes the development of antifungal effector mechanisms, and contributes to the containment of fungal growth. Our results indicate that F. pedrosoi is sensed by the NLRP3 inflammasome, which induces caspase-1 activation and production of IL-18. Moreover, IL-18 plays a crucial role in activating Th1 cells and controlling fungal loads during chromoblastomycosis. Further research into the mechanisms underlying IL-18-mediated immunity may lead to the development of novel therapeutic approaches for the treatment of this chronic fungal infection.
2018-02-26 | Transformation of Fonsecaea pedrosoi into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-γ production
Fonsecaea pedrosoi (F. pedrosoi) is the most common agent of chromoblastomycosis. Transformation of this fungus from its saprophytic phase into pathogenic sclerotic cells in tissue is an essential link to the refractoriness of this infection. Experimental studies in murine models have shown that the absence of CD4+ T cells impairs host defense against F. pedrosoi infection. Clinical research has also suggested that a relatively low level of the Th1 cytokine INF-γ and inefficient T cell proliferation are simultaneously present in patients with severe chromoblastomycosis upon in vitro stimulation with ChromoAg, an antigen prepared from F. pedrosoi. In the present study, we show that in mice intraperitoneally infected with F. pedrosoi-spores, -hyphae or in vitro-induced sclerotic cells respectively, the transformation of this causative agent into sclerotic cells contributes to a compromised Th1 cytokine production in the earlier stage of infection with impaired generation of neutrophil reactive oxygen species (ROS) and pan-inhibition of Th1/Th2/Th17 cytokine production with disseminated infection in the later stage by using a CBA murine Th1/Th2/Th17 cytokine kit. In addition, we have further demonstrated that intraperitoneal administration of recombinant mouse IFN-γ (rmIFN-γ) effectively reduces the fungal load in the infected mouse spleen, and dampens the peritoneal dissemination of F. pedrosoi-sclerotic cells. Meanwhile, exogeneous rmIFN-γ contributes to the formation and maintenance of micro-abscess and restores the decrease in neutrophil ROS generation in the mouse spleen infected with F. pedrosoi-sclerotic cells. Of note, we have once again demonstrated that it is a chitin-like component, but not β-glucans or mannose moiety, that exclusively accumulates on the outer cell wall of F. pedrosoi-sclerotic cells which were induced in vitro or isolated from the spleens of intraperitoneally infected BALB/c mice. In addition, our results indicate that decreased accumulation of chitin on the surface of live F. pedrosoi-sclerotic cells after chitinase treatment can be self-compensated in a time-dependent manner. Importantly, we have for the first time demonstrated that exclusive accumulation of chitin on the transformed sclerotic cells of F. pedrosoi is involved in an impaired murine Th1 cytokine profile, therefore promoting the refractoriness of experimental murine chromoblastomycosis.
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