The bacterial effector-mediated inhibition of caspase-1 activation

在这项工作中，我们发现NLRP3和NLRC4炎症小体在副溶血性弧菌感染时均被耐热性直接溶血素（TDHs）和III型分泌系统1 （T3SS1）激活。激活的炎性小体随后触发半胱天冬酶-1的激活，半胱氨酸蛋白酶对il -1 β的加工和释放至关重要。然而，细菌也有通过T3SS1抑制炎性体激活的功能。我们发现T3SS1分泌的效应蛋白VopQ和VopS主要阻止NLRC4炎性体的激活。VopQ和VopS分别诱导自噬和Rho gtpase（包括Cdc42）失活，这些细胞事件干扰斑点的组装，斑点是炎性体激活的平台。总的来说，基于T3SS1效应的炎症小体激活抑制可能为细菌逃避炎症小体介导的宿主免疫反应提供重要的见解。

In this work we found that both the NLRP3 and NLRC4 inflammasomes are activated by thermostable direct hemolysins (TDHs) and type III secretion system 1 (T3SS1) in response to V. parahaemolyticus infection. The activated inflammasomes then triggers the activation of caspase-1, a cysteine protease that is essential for IL-1beta processing and release. However, the bacteria also have a function to suppress inflammasome activation via T3SS1. We identified T3SS1 secreted effector proteins, VopQ and VopS, prevent mainly NLRC4 inflammasome activation. VopQ and VopS induce autophagy and the inactivation of Rho GTPases, including Cdc42, respectively, and these cellular events interfere with the assembly of specks, the platform of inflammasome activation. Collectively, T3SS1 effector-based suppression of inflammasome activation may provide important insights into bacterial strategies for evading inflammasome-mediated host immune responses.