Cell death pathways and their impact on host susceptibililty to intracelular pathogens

• Grant number: 13/50374-4
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2013
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: Consortium of Alberta, Laval, Dalhousie and Ottawa (CALDO)
• Principal Investigator: Karina Ramalho Bortoluci
• Grantee: Karina Ramalho Bortoluci
• Principal researcher abroad: Subash Sad
• Institution abroad: University of Ottawa (uOttawa), Canada
• Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 08/50958-8 - Interaction between innate immune receptors in the activation of macrophages and dendritic cells, AP.JP

Abstract

Immune system controls pathogens by mounting a rapid innate and acquired immune response, however, some pathogens such as Salmonella species are profoundly evasive and virulent, and cause a spectrum of disease from typhoid to gastroenteritis. Intracellular replication of ST and the consequent death of infected cells are considered as important mechanisms of virulence. Proteins often congregate into clusters as signalosomes to modulate cell fate. Although programmed cell death operates mainly through apoptosis and is considered non-inflammatory, previous results in our laboratories indicate that infected cells may also die by alternative mechanisms such as necroptosis and cathepsin-mediated cell death, which may lead to excessive inflammation. In this proposal we plan to evaluate the molecular checkpoints in the various cell death pathways using various mutants of Salmonella and macrophages that are deficient in key cell death pathways. We will use various cell biological, molecular and imaging procedures to identify the inter-relationship between these alternative mechanisms of cell death pathways. The project proposal builds on our relative, complimentary expertise and will foster the development of long-term collaboration in chronic inflammatory diseases. (AU)