Involvement of the NLRP3 Inflammasome in Innate and Humoral Adaptive Immune Responses to Fungal β-Glucan
Involvement of the NLRP3 Inflammasome in Innate and Humoral Adaptive Immune Responses to Fungal β-Glucan
复制标题
DOI：
10.4049/jimmunol.0902477
复制
发表时间：
2009-12-15
影响因子：
4.4
通讯作者：
Kawai, Taro
中科院分区：
文献类型：
--
作者：
Kumar, Himanshu;Kumagai, Yutaro;Kawai, Taro
真菌β-葡聚糖，如凝胶多糖，触发抗真菌先天免疫反应以及形成适应性免疫反应。在这项研究中，我们确定了一个关键途径，夫妇可得兰免疫反应。Curdlan通过NLRP 3炎性体促进树突状细胞和巨噬细胞产生促炎细胞因子IL-1 β。用白色念珠菌和酿酒酵母刺激也触发了NLRP 3炎性小体介导的IL-1 β产生。在体内，NLRP 3是需要有效的Ag-特异性抗体的生产时，可得兰作为一种佐剂，而它是无效的诱导Th 1和Th 17细胞分化。此外，用凝胶多糖诱导的CD 69上调和IgM产生刺激纯化的B细胞，而用其他NLRP 3炎性体激活剂如二氧化硅和铝盐刺激则没有。值得注意的是，这种诱导需要NLRP 3，但不依赖于Toll样受体和IL-1受体家族信号传导，表明在负责Ab应答的B细胞中存在NLRP 3依赖性和IL-1受体家族独立性机制。总的来说，这些发现揭示了NLRP 3炎性体在调节抗真菌先天免疫应答以及B细胞活化中的关键作用。免疫学杂志，2009，183：8061-8067.
Fungal beta-glucan, such as curdlan, triggers antifungal innate immune responses as well as shaping adaptive immune responses. In this study, we identified a key pathway that couples curdlan to immune responses. Curdlan promoted the production of the proinflammatory cytokine IL-1 beta by dendritic cells and macrophages through the NLRP3 inflammasome. Stimulation with Candida albicans and Saccharomyces cerevisiae also triggered the NLRP3 inflammasome-mediated IL-1 beta production. In vivo, NLRP3 was required for efficient Ag-specific Ab production when curdlan was used as an adjuvant, whereas it was dispensable for the induction of Th1 and Th17 cell differentiation. Furthermore, stimulation of purified B cells with curdlan-induced CD69 up-regulation and IgM production while stimulation with other NLRP3 inflammasome activators, such as silica and aluminum salt, did not. Notably, this induction required NLRP3 but was independent of Toll-like receptor and IL-1 receptor family signaling, suggesting the presence of NLRP3-dependent and IL-1 receptor family independent mechanisms in B cells responsible for Ab responses. Collectively, these findings reveal a critical role for the NLRP3 inflammasome in the regulation of antifungal innate immune responses as well as B cell activation. The Journal of Immunology, 2009, 183: 8061-8067.