Objective:

To investigate the role of chitin accumulation in modulating NLRP3 activation and its effect on fungal persistence in chromoblastomycosis caused by Fonsecaea pedrosoi.

Approach:

• Human Lesion Analysis: Analyzed human chromoblastomycosis lesions using immunohistochemistry and RT-PCR for cytokine transcripts.
• Mouse Models: Footpad-inoculated WT and NLRP3–/– mice with F. pedrosoi muriform cells for in vivo assessment.
• Cytokine Quantification: Used flow cytometric bead array to quantify cytokines in footpad homogenates and stimulated BMDM supernatants.
• NLRP3 Pathway Activation: Confirmed NLRP3 pathway activation in BMDMs via western blotting and immunofluorescence.

Key Findings:

• Muriform cells persisted in human lesions despite robust NLRP3 expression and elevated cytokines.
• In WT mice, lesions transitioned from purulent to granulomatous, with declining cytokine levels over time.
• In NLRP3–/– mice, IL-1β and IL-17A were produced independently of NLRP3 and did not decline.
• Chitin accumulation on muriform cells suppressed NLRP3 activation, reducing inflammatory responses.

Interpretation:

NLRP3 is involved in host defense against muriform cells, but chitin accumulation may inhibit its activation, contributing to chronic infection.

Limitations:

• Study primarily focused on muriform cells and may not fully represent other fungal forms.
• Limited sample size for human lesion analysis.

Conclusion:

Chitin accumulation on muriform cells may reduce NLRP3 activation, which could contribute to the chronic nature of chromoblastomycosis.