Role of necroptosis and pyroptosis in peritoneal macrophage dynamics in response to B16F0 melanoma cell line

• Grant number: 23/12818-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Gustavo Pessini Amarante Mendes
• Grantee: Laisa Maria Dantas Fernandes de Santana
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Macrophages are cells that are found in all tissues of the body and that act in various ways on the immune system, for instance, through recognition, phagocytosis and destruction of microorganisms, as well as regulating inflammation and tissue repair. From specific stimuli, these cells differentiate and play their role according to the tissue in which they are present. Interestingly to our project, two macrophage subpopulations, namely LPM and SPM, coexist in the peritoneal cavity, displaying different morphology, function and origin. In addition, infected/stimulated macrophages can undergo programmed cell deaths, such as apoptosis, pyroptosis and necroptosis, with pathophysiological consequences for the organism. Pro-inflammatory cell death programs are regulated by either RIPK3 (necroptosis) or Caspase-1/11 (pyroptosis) and executed by MLKL (necroptosis) and GSDMD (pyroptosis). Despite the vast amount of data on the characterization of macrophages and cell death processes, not much is known about the dynamics and function of peritoneal macrophages in animals genetically modified for the above-mentioned proteins. This project aims to characterize the subpopulation of peritoneal exudate cells, including the LPMs and SPMs in mice deficient for RIPK3, Caspase-1/11, MLKL or GSDMD before and after inoculation of the murine melanoma cell line B16F0 in the peritoneal cavity.