Cutting edge: nucleotide-binding oligomerization domain 1-dependent responses account for murine resistance against Trypanosoma cruzi infection.
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.
Silva
Grace K
GK
Department of Cell Biology, University of São Paulo, School of Medicine Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
Gutierrez
Fredy R S
FR
Guedes
Paulo M M
PM
Horta
Catarina V
CV
Cunha
Larissa D
LD
Mineo
Tiago W P
TW
Santiago-Silva
Juliana
J
Kobayashi
Koichi S
KS
Flavell
Richard A
RA
Silva
João S
JS
Zamboni
Dario S
DS
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*
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