title: A Yersinia effector protein promotes virulence by preventing inflammasome recognition of the type III secretion system.
abstract: 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.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. igor.brodsky@yale.edu
authors.forename: Igor E
authors.initials: IE
authors.lastname: Brodsky
authors.forename: Noah W
authors.initials: NW
authors.lastname: Palm
authors.forename: Saheli
authors.initials: S
authors.lastname: Sadanand
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Ryndak
authors.forename: Fayyaz S
authors.initials: FS
authors.lastname: Sutterwala
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: James B
authors.initials: JB
authors.lastname: Bliska
authors.forename: Ruslan
authors.initials: R
authors.lastname: Medzhitov
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D057131:Immune Evasion; D026901:Membrane Transport Proteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D014774:Virulence; D037521:Virulence Factors / Q000502:physiology*; D015007:Yersinia / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C435692:NLRC4 protein, human; C453881:NLRP3 protein, human; D037521:Virulence Factors; D020170:Caspase 1