Please use this identifier to cite or link to this item: http://www.arca.fiocruz.br/handle/icict/8127
Title: Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi
Authors: Caetano, Braulia Costa
Carmo, Bianca B.
Melo, Mariane Bandeira de
Cerny, Anna
Santos, Sara Lopes dos
Bartholomeu, Daniella Castanheira
Golenbock, Douglas Taylor
Gazzinelli, Ricardo Tostes
Affilliation: University of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USA
University of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USA
University of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USA
University of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USA
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, Brazil
University of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USA
University of Massachusetts. Medical School. Division of Infectious Disease and Immunology.Worcester, MA, USA/Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil
Abstract: UNC93B1 associates with Toll-Like Receptor (TLR) 3, 7 and 9, mediating their translocation from the endoplasmic reticulum to the endolysosome, thus allowing proper activation by microbial nucleic acids. We found that the triple deficient ‘3d’ mice, which lack functional UNC93B1 as well as functional endossomal TLRs, are highly susceptible to infection with Trypanosoma cruzi. The enhanced parasitemia and mortality in 3d animals were associated with impaired pro-inflammatory response, including reduced levels of IL-12p40 and IFN-γ. Importantly, the phenotype of 3d mice was intermediary between MyD88−/−(highly susceptible) and TLR9−/−(less susceptible), indicating the involvement of an additional UN93B1-dependent-TLR(s) on host resistance to T. cruzi. Hence, our experiments also revealed that TLR7 is a ritical innate immune receptor involved in recognition of parasite RNA, induction of IL-12p40 by dendritic cells, and consequent IFN-γby T lymphocytes. Furthermore, we show that upon T. cruzi infection triple TLR3/7/9−/−mice had similar phenotype than 3d mice. These data imply hat the nucleic acid-sensing TLRs are critical determinants of host resistance to primary infection with T. cruzi.
Keywords: Trypanosoma cruzi
Toll-Like Receptor
Issue Date: 2011
Publisher: American Association of Immunologists
Citation: CAETANO, Braulia Costa et al. Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi. J Immunol, 187(4): 1903-1911, 2011.
ISSN: 0022-1767
Copyright: open access
Appears in Collections:IRR - Artigos de Periódicos



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