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The participation of innate immunity receptors in the response to Trichophyton rubrum.

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Author(s):
Fábio Seiti Yamada Yoshikawa
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
Defense date:
Examining board members:
Sandro Rogerio de Almeida; Cyro Alves de Brito; Niels Olsen Saraiva Câmara; Carlos Pelleschi Taborda
Advisor: Sandro Rogerio de Almeida
Abstract

Dermatophytosis are chronic fungal infections whose main causative agent is Trichophyton rubrum. Despite its high incidence worldwide, the immunological mechanisms underlying these infections remain largely unknown. Here we investigated the involvement of two classes of innate immune receptors (NLRs and CLRs) in the reponse to T.rubrum and performed a proteomic profiling of macrophages upon T.rubrum stimulation. We observed that T.rubrum was able to drive NLRP3 inflammasome-derived IL-1β production and highlighted IL-1 signaling as an important component in the shaping of the IL-17 response. We defined the CLRs dectin-1 and dectin-2 as key receptors for the induction of inflammatory cytokines and for the infection control in the in vivo settings. Curiously, IL-17 cytokines and T and B lymphocytes were dispensable for fungal clearance. In addition, we uncovered CLEC1A as a new receptor in fungal sensing, involved in the recognition of T.rubrum glycolipids. Finally, the proteomic analysis revealed Vimentin and Plastin-2 as two proteins potentially involved in the host-pathogen interaction. (AU)

FAPESP's process: 12/14684-6 - The role of the inflammasome in a murine model of infection with Trichophyton rubrum: activation pathways and in vivo relevance
Grantee:Fábio Seiti Yamada Yoshikawa
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)