Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Eur J Immunol. 2011 Aug;41(8):2260-8. doi: 10.1002/eji.201041226. Epub 2011 Jul 4.
The Nlrp3 inflammasome has been proposed to play an important role in antifungal host defense. However, studies exploring the role of the inflammasome in antifungal host defense have been limited to the direct effects on IL-1β processing. Although IL-1β has important direct effects on the innate immune response, important effects of the caspase-1-dependent cytokines IL-1β and IL-18 are exerted on the initiation of the adaptive Th1 and Th17 cellular responses. No studies have been employed to assess the impact of the inflammasome on the Th1/Th17 defense mechanisms in vivo during candidiasis. In the present study, we demonstrate an essential role for caspase-1 and ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) in disseminated candidiasis through regulating antifungal Th1 and Th17 responses. Caspase-1(-/-) and ASC(-/-) mice display diminished Th1/Th17 responses, followed by increased fungal outgrowth and lower survival. These observations identify a critical role for the inflammasome in controlling protective adaptive immune responses during invasive fungal infection.
Nlrp3 炎性小体被认为在抗真菌宿主防御中发挥重要作用。然而，研究炎性小体在抗真菌宿主防御中的作用仅限于对 IL-1β 加工的直接影响。尽管 IL-1β 对先天免疫反应有重要的直接影响，但 caspase-1 依赖性细胞因子 IL-1β 和 IL-18 的重要作用在于启动适应性 Th1 和 Th17 细胞反应。目前还没有研究评估炎性体在念珠菌病期间体内 Th1/Th17 防御机制中的影响。在本研究中，我们通过调节抗真菌 Th1 和 Th17 反应，证明了 caspase-1 和 ASC（含有半胱天冬酶募集域的凋亡相关斑点样蛋白）在播散性念珠菌病中的重要作用。Caspase-1(-/-)和 ASC(-/-)小鼠表现出 Th1/Th17 反应减弱，随后真菌生长增加，存活率降低。这些观察结果表明，炎性体在控制侵袭性真菌感染期间保护性适应性免疫反应中起着关键作用。
