Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD 4878, Australia.
College of Public Health, Medical and Veterinary Sciences, James Cook University, Smithfield, QLD 4878, Australia.
Cell Rep. 2018 Apr 24;23(4):1085-1098. doi: 10.1016/j.celrep.2018.03.097.
Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1β. However, the roles for inflammasomes during parasitic helminth infections remain unclear. We demonstrate that mice and humans infected with gastrointestinal nematodes display increased IL-18 secretion, which in Trichuris-infected or worm antigen-treated mice and in macrophages co-cultured with Trichuris antigens or exosome-like vesicles was dependent on the NLRP3 inflammasome. NLRP3-deficient mice displayed reduced pro-inflammatory type 1 cytokine responses and augmented protective type 2 immunity, which was reversed by IL-18 administration. NLRP3-dependent suppression of immunity partially required CD4 cells but was apparent even in Rag1 mice that lack adaptive immune cells, suggesting that NLRP3 influences both innate and adaptive immunity. These data highlight a role for NLRP3 in limiting protective immunity to helminths, suggesting that targeting the NLRP3 inflammasome may be an approach for limiting the disease burden associated with helminth infections.
炎性小体通过调节 IL-1 家族细胞因子（如 IL-18 和 IL-1β）的功能来促进对微生物病原体的免疫。然而，炎性小体在寄生性蠕虫感染中的作用尚不清楚。我们证明，感染胃肠道线虫的小鼠和人类表现出 IL-18 分泌增加，这种增加在感染旋毛虫或蠕虫抗原的小鼠以及与旋毛虫抗原或类外泌体小泡共培养的巨噬细胞中依赖于 NLRP3 炎性小体。NLRP3 缺陷型小鼠表现出促炎型 1 型细胞因子反应减少和保护性 2 型免疫增强，而 IL-18 的给予则逆转了这种情况。NLRP3 依赖性免疫抑制部分需要 CD4 细胞，但即使在缺乏适应性免疫细胞的 Rag1 小鼠中也很明显，这表明 NLRP3 影响先天免疫和适应性免疫。这些数据突出了 NLRP3 在限制对蠕虫的保护性免疫中的作用，表明靶向 NLRP3 炎性小体可能是一种限制与蠕虫感染相关的疾病负担的方法。
