NLRP6是新近发现的胞内模式识别受体，然而其在抗感染免疫与炎症中的功能仍不清楚。预实验结果显示，铜绿假单胞菌感染小鼠角膜可诱导NLRP6表达，而沉默NLRP6使角膜促炎因子表达和荷菌量上调，角膜溃疡加重，提示NLRP6可能通过抑制炎症、促进细菌清除，介导角膜保护作用。那么，NLRP6介导免疫调控的分子机制是什么？体外实验发现，NLRP6能特异性抑制NLRP3炎症小体活化。我们先前报道，NLRP3炎症小体可以放大炎症，抑制巨噬细胞对铜绿假单胞菌的清除。结合文献报道和预实验结果，我们提出“NLRP6通过抑制经典NF-kB通路和竞争结合接头分子MAVS/ASC来负调控NLRP3炎症小体，从而抑制过度炎症、促进细菌清除，保护角膜”的假说，并拟通过动物模型和体外实验，从正、反两方面揭示NLRP6介导角膜保护的免疫调控机制及其负调控NLRP3炎症小体的分子机制，为角膜炎防治提供新的靶点和理论依据。

NLRP6 is a newly identified cytosolic pattern recognition receptor, whereas its role in anti-infectious immunity and inflammatory response remains unclear. Our preliminary data showed that Pseudomonas aeruginonsa (PA) infection induced NLRP6 expression in mouse corneas. In vivo knockdown of NLRP6 exacerbated corneal ulceration after PA infection, with increased pro-inflammatory cytokine expression and bacterial load, indicating that NLRP6 may play a protective role in bacterial keratitis (corneal infection) by suppressing corneal inflammation and enhancing bacterial elimination. Next question is, what is the underlying mechanism of NLRP6-mediated corneal resistance? In vitro experiments suggested that NLRP6 specifically inhibited activation of NLRP3 inflammasome. Our previous study reported that activation of NLRP3 inflammasome amplified the inflammatory response, and suppressed macrophage-mediated bacterial clearance of PA. Based on the literature and our preliminary data, we proposed a new hypothesis that NLRP6 negatively regulates NLRP3 inflammasome activation by suppressing canonical NF-kB pathway and competitively interacting with the adaptor molecules MAVS and ASC, therefore enhances bacterial elimination and reduces corneal inflammation, which finally leads to corneal resistance to PA infection. This project is designed to explore the role and molecular regulatory mechanism of NLRP6 in corneal anti-infectious immunity and NLRP3 inflammasome activation. Our findings may provide new targets and strategy for prevention and clinical treatment of bacterial keratitis.