Department of Cell Biology, University of São Paulo, School of Medicine Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
J Immunol. 2010 Feb 1;184(3):1148-52. doi: 10.4049/jimmunol.0902254. Epub 2009 Dec 30.
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.
有效的先天免疫识别细胞内原生动物寄生虫克氏锥虫对于宿主抵抗恰加斯病（一种严重的慢性疾病，影响拉丁美洲数百万人）至关重要。在这项研究中，我们评估了核苷酸结合寡聚化结构域（Nod）样受体蛋白在宿主对克氏锥虫感染的反应中的参与情况，发现 Nod1 依赖性，但不是 Nod2 依赖性反应，对于宿主抵抗感染是必需的。来自 Nod1(-/-) 小鼠的骨髓来源的巨噬细胞在感染时显示出 NF-κB 依赖性产物诱导的受损，并且在 IFN-γ存在下未能限制克氏锥虫感染。尽管血清中的细胞因子产生正常，但 Nod1(-/-) 小鼠对克氏锥虫感染非常敏感，与 MyD88(-/-) 和 NO 合酶 2(-/-) 小鼠相似。这些研究表明，Nod1 依赖性反应通过独立于细胞因子产生的机制来解释宿主对克氏锥虫感染的抵抗。
