Analysis of the role of CD11c+ cells in the immune response in experimental paracoccidioidomycosis

• Grant number: 14/16551-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2014
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Sandro Rogerio de Almeida
• Grantee: Suelen Silvana dos Santos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Paracoccidioidomycosis (PCM) is an endemic disease in Latin America and the most frequent systemic mycosis in Brasil. Resistent (A/J) mice are more efficient in the induction of a Th1-like phenotype in vitro and in vivo than susceptible (B10.A) mice. Great amounts of IL-10 are produced by pulmonary dendritic cells (DCs) from infected B10.A mice, but not by DCs from A/J mice. In addition, bone marrow derived DCs (BMDCs) from B10.A mice produce high levels of IL-12, TNF± and IL-1² in response to P. brasiliensis, and are able to induce anergy in naïve T cells. On the other hand, BMDCs from A/J mice secrete pro-inflammatory cytokines but also significant levels of TGF² and promote proliferation of regulatory T cells. The importance of DCs in the triggering of the immune response against different pathogens can be investigated in CD11c+ cells depletion models, but this approach has never been applied in the study of PCM. Therefore, the aim of this work is to characterize the immunological and cellular profile in the lung and lymph nodes of mice infected with P. brasiliensis after CD11c+ cells depletion, and how the lack of this population interferes in the infection outcome. The answers to these questions will provide a better understanding of the innate and adaptive response in experimental PCM. (AU)