The bacterial effector-mediated inhibition of caspase-1 activation

点击翻译按钮获取中文摘要

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.