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

• Grant number: 18/23229-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2018
• End date: November 30, 2019
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Larissa Dias da Cunha
• Grantee: Douglas dos Santos
• Host 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.