Impaired Innate Immunity in Tlr4(-/-) Mice but Preserved CD8(+) T Cell Responses against Trypanosoma cruzi in Tlr4-, Tlr2-, Tlr9- or Myd88-Deficient Mice

Impaired Innate Immunity in Tlr4(-/-) Mice but Preserved CD8(+) T Cell Responses against Trypanosoma cruzi in Tlr4-, Tlr2-, Tlr9- or Myd88-Deficient Mice

Autor Oliveira, Ana-Carolina Google Scholar
Alencar, Bruna C. de Autor UNIFESP Google Scholar
Tzelepis, Fanny Autor UNIFESP Google Scholar
Klezewsky, Weberton Google Scholar
Silva, Raquel N. da Google Scholar
Neves, Fabieni S. Google Scholar
Cavalcanti, Gisele S. Google Scholar
Boscardin, Silvia Google Scholar
Nunes, Marise P. Google Scholar
Santiago, Marcelo F. Google Scholar
Nobrega, Alberto Google Scholar
Rodrigues, Mauricio M. Autor UNIFESP Google Scholar
Bellio, Maria Google Scholar
Instituição Universidade Federal do Rio de Janeiro (UFRJ)
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Inst Osvaldo Cruz IOC FIOCRUZ Rio de Janeiro
Resumo The murine model of T. cruzi infection has provided compelling evidence that development of host resistance against intracellular protozoans critically depends on the activation of members of the Toll-like receptor (TLR) family via the MyD88 adaptor molecule. However, the possibility that TLR/MyD88 signaling pathways also control the induction of immunoprotective CD8(+) T cell-mediated effector functions has not been investigated to date. We addressed this question by measuring the frequencies of IFN-gamma secreting CD8(+) T cells specific for H-2K(b)-restricted immunodominant peptides as well as the in vivo Ag-specific cytotoxic response in infected animals that are deficient either in TLR2, TLR4, TLR9 or MyD88 signaling pathways. Strikingly, we found that T. cruzi-infected Tlr2(-/-), Tlr4(-/-), Tlr9(-/-) or Myd88(-/-) mice generated both specific cytotoxic responses and IFN-gamma secreting CD8(+) T cells at levels comparable to WT mice, although the frequency of IFN-gamma(+)CD4(+) cells was diminished in infected Myd88(-/-) mice. We also analyzed the efficiency of TLR4-driven immune responses against T. cruzi using TLR4-deficient mice on the C57BL genetic background (B6 and B10). Our studies demonstrated that TLR4 signaling is required for optimal production of IFN-gamma, TNF-alpha and nitric oxide (NO) in the spleen of infected animals and, as a consequence, Tlr4(-/-) mice display higher parasitemia levels. Collectively, our results indicate that TLR4, as well as previously shown for TLR2, TLR9 and MyD88, contributes to the innate immune response and, consequently, resistance in the acute phase of infection, although each of these pathways is not individually essential for the generation of class I-restricted responses against T. cruzi.
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Número do financiamento CNPq: 420067/2005-1
Data de publicação 2010-04-01
Publicado em Plos Pathogens. San Francisco: Public Library Science, v. 6, n. 4, 16 p., 2010.
ISSN 1553-7366 (Sherpa/Romeo, fator de impacto)
Publicador Public Library Science
Extensão 16
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000277722400042
Endereço permanente

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