AUTHOR=Wang Xiaolin , Sun Jin , Wan Luming , Yang Xiaopan , Lin Haotian , Zhang Yanhong , He Xiang , Zhong Hui , Guan Kai , Min Min , Sun Zhenxue , Yang Xiaoli , Wang Bin , Dong Mingxin , Wei Congwen 

TITLE=The Shigella Type III Secretion Effector IpaH4.5 Targets NLRP3 to Activate Inflammasome Signaling

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.511798

DOI=10.3389/fcimb.2020.511798

ISSN=2235-2988

ABSTRACT=<p>Activation of the NLRP3 inflammasome requires the expression of NLRP3, which is strictly regulated by its capacity to directly recognize microbial-derived substances. Even though the involvement of caspase-1 activation in macrophages <italic>via</italic> NLRP3 and NLRC4 has been discovered, the accurate mechanisms by which <italic>Shigella</italic> infection triggers NLRP3 activation remain inadequately understood. Here, we demonstrate that IpaH4.5, a <italic>Shigella</italic> T3SS effector, triggers inflammasome activation by regulating NLRP3 expression through the E3 ubiquitin ligase activity of IpaH4.5. First, we found that IpaH4.5 interacted with NLRP3. As a result, IpaH4.5 modulated NLRP3 protein stability and inflammasome activation. Bacteria lacking IpaH4.5 had dramatically reduced ability to induce pyroptosis. Our results identify a previously unrecognized target of IpaH4.5 in the regulation of inflammasome signaling and clarify the molecular basis for the cytosolic response to the T3SS effector.</p>