Bacterial pathogens utilize pore-forming toxins or specialized secretion systems to deliver virulence factors to modulate host cell physiology and promote bacterial replication. Detection of these secretion systems or toxins, or their activities, by nucleotide-binding oligomerization domain leucine-rich repeat proteins (NLRs) triggers the assembly of inflammasomes, multiprotein complexes necessary for caspase-1 activation and host defense. Here we demonstrate that caspase-1 activation in response to the Yersinia type III secretion system (T3SS) requires the adaptor ASC and involves both NLRP3 and NLRC4 inflammasomes. Further, we identify a Yersinia type III secreted effector protein, YopK, which interacts with the T3SS translocon to prevent cellular recognition of the T3SS and inflammasome activation. In the absence of YopK, inflammasome sensing of the T3SS promotes bacterial clearance from infected tissues in vivo. These data demonstrate that a class of bacterial proteins interferes with cellular recognition of bacterial secretion systems and contributes to bacterial survival within host tissues.
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