Role of the Leishmania RNA virus (LRV1-4) present in Leishmania guyanensis M4147 strain in the modulation of the innate immune response

• Grant number: 15/25404-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2016
• End date: September 30, 2019
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Renan Villanova Homem de Carvalho
• 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

Leishmaniasis is constituted by a wide spectrum of diseases caused by protozoan from Leishmania gender, which comprehenses many species, responsible for the different forms of the disease. In Brazil, the most commom form of the disease é causes American tegumentary leishmaniasis (ATL), found all across the country, and is caused by the species L. braziliensis, L. panamensis and L. guyanensis. Protection against the disease is related with a Th1 immune response profile, with great induction of IFN-gamma, which activates macrophages, inducing nitric oxide synthesis. The role of pattern recognition receptors (PRRs) like TLRs and NLRs in the induction of a protective Th1 response has already been shown to be extremely important for the elimination of intracellular parasites, like Leishmania. However, some pathogens evolved in order to create evasion mechanisms, that allow them to escape from immune recognition. In the specific case of Leishmania guyanensis, it was shown some decades ago that these parasites may present a double-stranded RNA virus inside them, which were denominated Leishmania RNA virus (LRVs). In experimental murine model, LRV from several clinical isolates of Leishmania guyanensis were shown to be capable of inducing a strong inflammatory reaction upon its ligation to TLR3, worsening the disease. Although this study has pointed out TLR3 as an important receptor for the detection and subsequent response to the virus, the mechanisms by which LRV contributes to a higher pathogenicity from Leishmania guyanensis are still poorly understood. Several articles show that Leishmania parasites are capable of activating TLRs, like TLR2, TLR3, TLR4 and TLR9. Hence, other studies show that some TLRs induce autophagy and modulate inflammasome assembly and activation. Recently, a work published by our group has shown that the NLRP3 inflammasome is essential to control Leishmania spp. infection. In this context, the current project aims to investigate the role of LRV1-4 in the regulation of inflammasome and innate immunity in general, as well as unraveling the molecular mechanisms involved in LRV1-4-dependent Leishmania guyanensis pathogenicity (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CARVALHO, Renan Villanova Homem de. The role of Leishmania RNA vírus in the modulation of the innate imune response. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.