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Role of pattern recognition receptors (PRRs) in the activation of macrophages in cutaneous fungal infections caused by Fonsecaea pedrosoi, Sporothrix schenckii and Trichophyton rubrum

Grant number: 12/18598-7
Support type:Research Projects - Thematic Grants
Duration: April 01, 2013 - March 31, 2016
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Sandro Rogerio de Almeida
Grantee:Sandro Rogerio de Almeida
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated grant(s):14/50326-2 - Pathogenicity of dermatophytes, AP.R
Associated scholarship(s):14/11146-9 - The role of neutrophils and Toll Like Receptors 2 and 4 in experimental chromoblastomycosis by F. pedrosoi, BP.DR
13/19213-4 - Study of interaction between macrophages opposite species Sporothrix brasiliensis, BP.DR


Fungi causing cutaneous mycoses, such as Trichophyton rubrum, Sporothrix schenckii and Fonseacaea pedrosoi are gaining prominent clinical importance due to its refractory character to current therapeutic approaches and the involvement of immunosuppressed patients, in whom the disease is more severe. Much of this framework is due to the little knowledge we have about the immunopathological mechanisms involved in the disease, which complicates the understanding of it, the development of new therapeutic strategies and detection of potential pharmacological targets. Recently, several studies have demonstrated the involvement of receptors of the innate immune response in the control of infectious diseases.The pattern recognition receptors (PRRs) and Nod (NLRs), Tolls and C-type lectins, are elements of the innate immune response-related survey of intra-and extracellular environment, recognizing pathogen associated molecular patterns (PAMPs) or damage to the host (DAMPS). When activated, the receptors can form inflamassomos, proteins platforms involved in the activation of caspase-1 and subsequently of proinflammatory cytokines such as TNF-±, IL-1² and IL-18.The activity of PRRs / Inflamassomos been linked to several pathophysiological processes, such as diabetes, obesity and infectious diseases (bacterial, viral and fungal). Particularly in the case of mycosis, information is still incipient but signal a fundamental role in the control and inflamassomos definition of a protective adaptive response (TH1 and TH17). Therefore, this project aims to clarify the immunological mechanisms involved in the interaction with PRRs important pathogenic fungi, and thus enable more knowledge of the pathophysiology of chromoblastomycosis, sporotrichosis and dermatophytosis. (AU)