Autophagy induction by Leishmania sp via innate immune receptors

• Grant number: 16/00494-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2016
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Warrison Athanásio Coelho de Andrade
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/04684-4 - The inflammasome in the host response against intracellular pathogens and the microbial mechanisms for its evasion, AP.TEM

Abstract

Leishmania parasites are the causative agent of leishmaniasis in humans, a disease that affects over 12 million people, and more than 350 million people are in risk of acquiring the disease worldwide. After being introduced into the skin by the mosquito bite, the promastigotes are phagocytosed by macrophages, neutrophils and dendritic cells, once internalized differentiate into amastigotes, which is able to replicate within phagolysosomes and negatively modulate several signaling pathways involved in the innate immunity activation. Upon recognition, the induction of the innate immune response (IL-12, TNF-± and IFN-³) is essential for the control of parasites. These cells express pattern recognition receptors (PRRs), such as TLRs and NLRs receptors, and recognize molecular patters present on the pathogens (PAMPs), leading to the activation of effective cellular responses. PRRs signaling induce the production of NO and ROS, which are the main effectors responsible for resistance to Leishmania infection. While the role of TLRs and NLRs in Leishmania detection is well established, the mechanism responsible for controlling and death of the parasite remains debatable. Autophagy can be induced via TLRs and NLRs, and plays an important role in the control of many intracellular pathogens such as viruses, bacteria, and the protozoan Toxoplasma gondii. In this proposal we will investigate the role of the innate immunity receptors in the induction of autophagy and its role in the control of Leishmania infection.