Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands
Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands
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DOI：
10.1002/eji.201040827
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发表时间：
2011-05-01
影响因子：
5.4
通讯作者：
Girardin, Stephen E.
中科院分区：
文献类型：
--
作者：
Magalhaes, Joao G.;Lee, Jooeun;Girardin, Stephen E.
胞壁酰肽是细菌肽聚糖的组成部分，其在哺乳动物中的生物学功能已被广泛研究。特别地，胞壁酰肽触发炎症，有助于宿主防御微生物感染，并调节对抗原的适应性免疫应答。这些细菌分子通过核苷酸寡聚化结构域1（Nod1）和Nod2检测，最近的证据表明胞壁酰二肽也激活NLRP 3和NLRP 1炎性小体。在这里，我们研究了Rip2的作用，Nod1和Nod2依赖性信号的适配器，在多个方面的主机响应胞壁肽在体内，如炎性细胞因子分泌，激活和招聘的巨噬细胞和中性粒细胞的注射部位，系统性激活骨髓，T和B细胞在脾脏，佐剂和能力，以避免适应性反应卵清蛋白。我们的研究结果表明，Rip2是至关重要的所有生物功能的研究。我们还鉴定了CD11c（int）CD11b（+）炎性树突状细胞作为体内响应Nod刺激的主要髓样细胞群体。总之，我们的研究结果突出了Rip2对先天性和适应性免疫的Nod依赖性诱导的重要性。
Muramyl peptides are the building blocks of bacterial peptidoglycan, and their biological functions in mammals have been extensively studied. In particular, muramyl peptides trigger inflammation, contribute to host defense against microbial infections, and modulate the adaptive immune response to antigens. These bacterial molecules are detected by nucleotide oligomerization domain 1 (Nod1) and Nod2, and recent evidence suggests that muramyl dipeptide also activates NLRP3 and NLRP1 inflammasomes. Here, we investigated the role of Rip2, the adaptor for Nod1- and Nod2-dependent signaling, in multiple aspects of the host response to muramyl peptides in vivo, such as inflammatory cytokine secretion, activation and recruitment of macrophages and neutrophils to the site of injection, systemic activation of myeloid, T and B cells in the spleen, adjuvanticity and capacity to polarize the adaptive response to ovalbumin. Our results demonstrate that Rip2 was crucial for all the biological functions studied. We also identified CD11c(int)CD11b(+) inflammatory dendritic cells as a major myeloid cell population responding to Nod stimulation in vivo. Together, our results highlight the importance of Rip2 for Nod-dependent induction of innate and adaptive immunity.