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Inflammasome and Inflammatory Programmed Cell Death in Chromoblastomycosis

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Abstract

Chromoblastomycosis (CBM) is a chronic, progressive fungal disease of the skin and subcutaneous tissue caused by a group of dematiaceous fungi. Verrucous lesions present parasite-rich granulomas and predominance of a Th2 patterns of cytokines. The inflammasome constitutes a macromolecular protein complex that play a role in the activation of caspase 1 that cleaves pro-IL1β and pro-IL18, essential mediators of inflammation, and also activates pyroptosis. We intended to explore the presence and a possible role of inflammasome elements in cutaneous human lesions in CBM, considering the expression of IL1β, IL18, caspase 1, NLRP1, and also RIPK3, a key downstream component of necroptosis signaling. 35 skin biopsies of cutaneous lesions of verrucous form of CBM and 10 biopsies from normal skin were selected. The diagnosis was based on histological and clinical analysis. An immunohistochemical protocol was performed. The histopathological analysis evidenced epidermis with hyperkeratosis, irregular acanthosis, and micro abscesses. The dermis presented suppurative granulomas and inflammatory infiltrate composed by giant cells, macrophages, epithelioid cells, lymphocytes, and some eosinophils. Positive cells were distributed in the inflammatory infiltrate, with an increased number of cells expressing caspase 1, IL1β and IL18. Cells expressing RIPK3 and NLRP1 were less frequent. The intense presence of caspase 1, IL1β and IL18, allied to NLRP1 expression, suggest that inflammasome and pyroptosis could play a role in the immune response against fungal agents of CBM. Our results, allied to data from literature, could suggest that inflammasome-mediated response and pyroptosis could be a target to be explored to decrease CBM lesions.

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Acknowledgements

CP—Research productivity grant of National Council for scientific and Technological Development (CNPq).

Funding

The authors declare there is no funding to the research. CP receives a research productivity grant of National Council for Scientific and Technological Development (CNPq).

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Authors and Affiliations

  1. Laboratório da Disciplina de Patologia de Moléstias Transmissíveis, Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil

    Carla Pagliari, Luciane Kanashiro-Galo & Mirian Nacagami Sotto

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  1. Carla Pagliari
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  2. Luciane Kanashiro-Galo
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  3. Mirian Nacagami Sotto
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Contributions

All authors contributed to the study conception and design. CP: conceptualization, project administration, methodology, writing. LK-G: methodology, review. MNS: formal analysis, review.

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Correspondence to Carla Pagliari.

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Ethical approval was waived by the local Ethics Committee of University of São Paulo, Medical School in view of the retrospective nature of the study and all the procedures being performed were part of the routine care. The use of the material that constituted the casuistic was approved under the number 0317/11.

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Pagliari, C., Kanashiro-Galo, L. & Sotto, M.N. Inflammasome and Inflammatory Programmed Cell Death in Chromoblastomycosis. Mycopathologia 188, 63–70 (2023). https://doi.org/10.1007/s11046-022-00679-w

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