Evaluation of the involvement of M1 and M2 macrophages in the response to the dimorphic fungus Paracoccidioides brasiliensis

• Grant number: 12/14828-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2012
• Effective date (End): February 29, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ronei Luciano Mamoni
• Grantee: Munir Regini Paião
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

ABSTRACTParacoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis (Pb) is the most important systemic mycosis affecting immunocompetent individuals in Brazil. Paracoccidioidomycosis presents two clinical forms: the acute or juvenile form (JF), characterized by a predominantly Th2 immune response, and the adult form (AF), localized, chronic and characterized by the predominance of Th1 response. It is still unclear which factors determine the adaptive immune response generated against Pb, but it may be possible that events occurring during the first contact with the fungus play an important role. Resident tissue macrophages and other cells of the innate immune response are the first cells recognizing the fungus through receptors such as TLRs and CLRs. Recent studies have led to more strict characterization of macrophages, which can be classified into two main subpopulations: macrophages M1 and M2. The M1 cells exhibit high production of iNOS, IL-23, IL-12, CXCL8 and CXCL9, whereas the M2 cells have a high production of IL-10, CD206 and CD301. Furthermore, these cells also differ in their microbicidal and anti-tumor activity and capacity to develop granulomas. Despite the fact that the role of macrophages (M1 or M2) in fungal infections is scarce, there are evidences pointing to the presence of different populations of macrophages in PCM. Previous studies have shown the presence of TNF-± and IL-23 produced by macrophages in the lesions of (AF) patients, which show granulomas formed by giant cells that produce nitric oxide. On the other hand, (JF) patients present loose granulomas, with macrophages producing IL-10 and few giant cells. These results were suggestive of the presence of different types of macrophages in the two clinical forms. Thus, it is possible that different types of macrophages present in two clinical forms can modulate the adaptive immune response leading to the resistance or susceptibility to disease that characterize the two clinical forms of paracoccidioidomycosis.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PAIÃO, Munir Regini. Evaluation of the participation of M1 and M2 macrophages in the immune response against the dimorphic fungus Paracoccidioides brasiliensis. 2016. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.