title: Cutting edge: nucleotide-binding oligomerization domain 1-dependent responses account for murine resistance against Trypanosoma cruzi infection.
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-kappaB-dependent products in response to infection and failed to restrict T. cruzi infection in presence of IFN-gamma. 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.
authors.affiliation: Department of Cell Biology, University of São Paulo, School of Medicine Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Silva
authors.forename: Fredy R S
authors.initials: FR
authors.lastname: Gutierrez
authors.forename: Paulo M M
authors.initials: PM
authors.lastname: Guedes
authors.forename: Catarina V
authors.initials: CV
authors.lastname: Horta
authors.forename: Larissa D
authors.initials: LD
authors.lastname: Cunha
authors.forename: Tiago W P
authors.initials: TW
authors.lastname: Mineo
authors.forename: Juliana
authors.initials: J
authors.lastname: Santiago-Silva
authors.forename: Koichi S
authors.initials: KS
authors.lastname: Kobayashi
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.forename: Dario S
authors.initials: DS
authors.lastname: Zamboni
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D053474:Nod1 Signaling Adaptor Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D051193:Toll-Like Receptors