Characterization of peritoneal macrophages in mice deficient in regulatory or effector proteins of necroptosis and pyroptosis

• Grant number: 22/03501-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2022
• End date: May 31, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Gustavo Pessini Amarante Mendes
• Grantee: Raiane Silva de Morais
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Macrophages are cells of the immune system found in all tissues of the body, with diverse functions that include recognition, phagocytosis, elimination of pathogens, and tissue repair. Such cells differentiate and specialize in tissues and produce unique responses. Interestingly, the coexistence of two subsets of tissue macrophages in the peritoneal cavity, namely LPMs and SPMs, was described as bearing distinct characteristics, development, and functions. Furthermore, macrophages can undergo regulated cell death, including apoptosis (non-inflammatory) and the two pro-inflammatory pathways - pyroptosis and necroptosis. Such pathways have regulatory and effector proteins essential for such processes, such as RIPK3 and MLKL in necroptosis, and Caspase-1/11 and GSDMD in pyroptosis. Although the characteristics of macrophages and cell death dynamics are widely described in the literature, the dynamics of peritoneal macrophages in animals genetically modified for the proteins mentioned above are still unknown. The project in question aims to characterize and describe the dynamics of LPMs and SPMs in response to an inflammatory stimulus in mice genetically deficient for the proteins RIPK3, MLKL, Caspase-1/11, and GSDMD. Therefore, characterization by flow cytometry of peritoneal macrophage subpopulations of these animals will be performed. As a result, we should be able to gain insight into the influence of cell death molecules on peritoneal macrophage dynamics and function.(AU)