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Evaluation of the AIM2 role in the innate immune response against Leishmania amazonensis

Grant number: 17/20687-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2018
Effective date (End): April 30, 2020
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Dario Simões Zamboni
Grantee:Leonardo Lima dos Santos
Home 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

The Leishmaniasis is a disease that afflicts around 12 million people around 98 countries. In addition, there are 350 other million people that live at zones with risk of infection. Several species of the genus Leishmania spp. might evoke this disease in the vertebrate hosts, such as in humans. These, when infected by the parasite of the species L. major, L. braziliensis and L. amazonensis develop the characteristic symptoms of the cutaneous leishmaniasis. Our group demonstrated that the NLRP3 inflammasome is important for the control of infection by L. amazonensis. However, the contribution of other inflammasomes for the response against the Leishmania spp. infection remains few understood. In this work, it was also demonstrated that the IL-1R deficiency leads to a higher susceptibility, to this parasite, than the NLRP3 deficiency. Suggesting that other inflammasomes, that operate via IL-1R, might be involved in the response to this pathogen. Among these, the AIM2 highlights as a cytosolic DNA sensor that after its activation promotes cell detah and the release of inflammatory cytokines as IL-1±, IL-1² e IL-18. Preliminary data, produced in our laboratory, support a important role of AIM2 in the recognition and control of the L. amazonensis infection. In addition, the cytokine IL-1± seems to be involved. Therefore, the aim of our work is to investigate the AIM2 role in the innate immune response against L. amazonensis, as well as the effector mechanisms that participate in the control of infection in macrophages and in vivo, after the activation of this sensor.

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