期刊
JOURNAL OF IMMUNOLOGY
卷 187, 期 4, 页码 1903-1911出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1003911
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资金
- Atlantic Philanthropies/Ludwig Institute for Cancer Research/Program of Clinical Discovery
- Instituto de Ciencia e Tecnologia de Vacinas/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)
- National Institutes of Health [R21 AI08097, R01 AI071319-01, R01 GM54060, R01 AI079293]
- World Health Organization/Special Program for Research and Training in Tropical Diseases
UNC93B1 associates with TLR3, 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 endosomal TLRs, are highly susceptible to infection with Trypanosoma cruzi. The enhanced parasitemia and mortality in 3d animals were associated with impaired proinflammatory response, including reduced levels of IL-12p40 and IFN-gamma. Importantly, the phenotype of 3d mice was intermediary between MyD88(-/-) (highly susceptible) and TLR9(-/-) (moderately 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 critical innate immune receptor involved in recognition of parasite RNA, induction of IL-12p40 by dendritic cells, and consequent IFN-gamma by T lymphocytes. Furthermore, we show that upon T. cruzi infection, triple TLR3/7/9(-/-) mice had similar phenotype than 3d mice. These data imply that the nucleic acid-sensing TLRs are critical determinants of host resistance to primary infection with T. cruzi. The Journal of Immunology, 2011, 187: 1903-1911.
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