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The role of HIF-1a and glycolytic metabolism in inflammatory polarization of deficients macrophages in LC3- associated phagocytosis

Grant number: 18/23229-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2018
Effective date (End): November 30, 2019
Field of knowledge:Biological Sciences - Immunology
Principal researcher:Larissa Dias da Cunha
Grantee:Douglas dos Santos
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Clearance of dying cells is a pivotal function of the immune system. During the process of phagocytosis of apoptotic cells some components of the autophagy machinery can be recruited, leading to the lipidation of LC3 in the phagosome membrane, which facilitates its maturation and fusion with the lysosome. This process is known as LC3-associated phagocytosis (LAP). We have recently established that LAP is pivotal in the immune response to engulfed apoptotic cells. LAP-deficient macrophages fail to degrade engulfed cellular corpses and their function polarizes to an inflammatory phenotype, unlike wild type cells. This inflammatory polarization reduces the immune suppressive function of tumor-associated macrophages, leading to more active T lymphocytes in the tumor microenvironment and reducing tumor growth. In this project, we propose to investigate the mechanisms driving inflammation in LAP-deficient macrophages upon engulfment of dying cells, focusing on the role of glycolytic metabolism and HIF-1a in this process.

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