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Cutting Edge: Nucleotide-Binding Oligomerization Domain 1-Dependent Responses Account for Murine Resistance against Trypanosoma cruzi Infection

2009; American Association of Immunologists; Volume: 184; Issue: 3 Linguagem: Inglês

10.4049/jimmunol.0902254

1550-6606

Grace K. Silva, Fredy R. S. Gutierrez, Paulo Marcos da Matta Guedes, Catarina V. Horta, Larissa D. Cunha, Tiago Wilson Patriarca Mineo, Juliana Santiago-Silva, Koichi S. Kobayashi, Richard A. Flavell, João S. Silva, Dario S. Zamboni,

Parasites and Host Interactions

Abstract An effective innate immune recognition of the intracellular protozoan parasite Trypanosoma cruzi is critical for host resistance against Chagas disease, a severe and chronic illness that affects millions of people in Latin America. In this study, we evaluated the participation of nucleotide-binding oligomerization domain (Nod)-like receptor proteins in host response to T. cruzi infection and found that Nod1-dependent, but not Nod2-dependent, responses are required for host resistance against infection. Bone marrow-derived macrophages from Nod1−/− mice showed an impaired induction of NF-κB–dependent products in response to infection and failed to restrict T. cruzi infection in presence of IFN-γ. Despite normal cytokine production in the sera, Nod1−/− mice were highly susceptible to T. cruzi infection, in a similar manner to MyD88−/− and NO synthase 2−/− mice. These studies indicate that Nod1-dependent responses account for host resistance against T. cruzi infection by mechanisms independent of cytokine production.