Journal
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2020.511798
Keywords
Shigella; IpaH4; 5; NLRP3; inflammasome; T3SS
Categories
Funding
- National Natural Science Foundation of China [81671973, 31670761, 31872715, 81773205]
- Beijing Natural Science Foundation [7182122, 5182029, 5182030]
- National Key Research and Development Program of China [2018YFC1603705, 2018YFA0900800]
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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 macrophagesviaNLRP3 and NLRC4 has been discovered, the accurate mechanisms by whichShigellainfection triggers NLRP3 activation remain inadequately understood. Here, we demonstrate that IpaH4.5, aShigellaT3SS 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.
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