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Role of IL-1 in the intestinal mucosal integrity and microbiota alterations during visceral leishmaniasis

Grant number: 19/12991-8
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): January 10, 2020
Effective date (End): January 09, 2021
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:João Santana da Silva
Grantee:Laís Amorim Sacramento
Supervisor abroad: Phillip A Scott
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : University of Pennsylvania, United States  
Associated to the scholarship:17/04347-6 - Cooperation between TLR4 and IL-1R signaling pathways in the regulation of immune response during human and murine l. infantum infection, BP.PD

Abstract

IL-1 affects many cells and organs and is an important immunity mediator. According to our results (FAPESP process Number 2017/04347-6), during the chronic phase of visceral leishmaniasis (VL), IL-1alpha is induced in the gut and promotes intestinal mucosal integrity through the induction of tight junctions to avoid microbiota translocation. Consequently, it prevented an exacerbated Th1 response in the mesenteric lymph nodes (mLN) and spleen. To advance in this knowledge, we propose collaboration with Prof. Dr. Phillip Scott from University of Pensilvania - USA. Professor Scott has experience in microbiome sequencing and bioinformatic analysis of Leishmania infected skin. In this sense, our project proposes to study the role of IL-1alpha in the intestinal mucosal integrity, focusing on the microbiota composition and the pattern of immune response generated in the gut during VL. More specifically, our objectives are: 1) To determine the composition of gut microbiota during VL; 2) To determine the contribution of IL-1 signaling in the epithelial cells and in the DCs in the gut homeostasis during the infection; 3) To evaluate the immune response in the lamina propria and mesenteric lymph nodes focusing on DCs subsets and Th1 response. Thus, the study of the relation between IL-1 and gut will clarify important immunophatological aspects that determine the severity of VL.