Fritz Jörg H, Le Bourhis Lionel, Sellge Gernot, Magalhaes Joao Gamelas, Fsihi Hafida, Kufer Thomas A, Collins Cathy, Viala Jérôme, Ferrero Richard L, Girardin Stephen E, Philpott Dana J
Department of Immunology, Medical Sciences Building, University of Toronto, 1 King's College Circle, M5S 1A8 Toronto, Ontario, Canada.
Immunity. 2007 Apr;26(4):445-59. doi: 10.1016/j.immuni.2007.03.009. Epub 2007 Apr 12.
Recent evidence has suggested that signals other than those from Toll-like receptors (TLRs) could contribute to the elicitation of antigen-specific immunity. Therefore, we examined the role of the Nod-like receptor (NLR) family member, Nod1, in the generation of adaptive immune responses. Our findings show that innate immune sensing of peptidoglycan by Nod1 is key for priming antigen-specific T cell immunity and subsequent antibody responses in vivo. Nod1 stimulation alone was sufficient to drive antigen-specific immunity with a predominant Th2 polarization profile. In conjunction with TLR stimulation, however, Nod1 triggering was required to instruct the onset of Th1 and Th2 as well as Th17 immune pathways. Cells outside of the hematopoietic lineage provided the early signals necessary to orchestrate the development of Nod1-dependent immune responses. These findings highlight Nod1 as a key innate immune trigger in the local tissue microenvironment that drives the development of adaptive immunity.
最近有证据表明，除了来自Toll样受体（TLR）的信号外，其他信号也可能有助于引发抗原特异性免疫。因此，我们研究了Nod样受体（NLR）家族成员Nod1在适应性免疫反应产生中的作用。我们的研究结果表明，Nod1对肽聚糖的天然免疫感知是体内启动抗原特异性T细胞免疫和随后抗体反应的关键。单独的Nod1刺激足以驱动具有主要Th2极化特征的抗原特异性免疫。然而，与TLR刺激相结合时，需要触发Nod1来指导Th1和Th2以及Th17免疫途径的启动。造血谱系以外的细胞提供了协调Nod1依赖性免疫反应发展所需的早期信号。这些发现突出了Nod1作为局部组织微环境中驱动适应性免疫发展的关键天然免疫触发因素。
