Relationship of endoplasmic reticulum stress, autophagy, inflammasome and nitric oxide production in inflammatory infectious processes

• Grant number: 16/14188-0
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): September 01, 2016
• Effective date (End): November 30, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Luiza Antunes de Castro Jorge
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

One of the aims of the CRID/CEPID project involves the characterization of the connection of endoplasmic reticulum (ER) stress, autophagy, inflammasome and nitric oxide production. We will evaluate the effect of the autophagy and ER stress separately into each process. This will be achieved by using gene knockdown and Atg5flox/flox/Lysm-Cre mice for autophagy evaluation during Leishmania infection, one of the main infectious disease agents focused in the AIMS of the CEPID/CRID project. For ER stress we will evaluate the effect of ER stress inhibitors over autophagy, inflammasome and nitric oxide production. In addition, we will study the mechanism behind this interplay. We will use mice knocked out for innate immune receptors to gain more insight into the signaling mechanism involved. We will use Leishmania as a model to study this connection once this pathogen can activate these four processes. Finally, we will initiate prospective studies using Zika virus as a secondary infection model. Zika virus is believed to trigger strong inflammatory responses, so we will evaluate whether the findings with Leishmania holds true for a different intracellular pathogen. The development of this project will contribute significantly to the understanding of the regulation of host response during infection by intracellular pathogens, integrating cellular stress response with components of innate immunity. (AU)