Vibrio parahaemolyticus effector proteins suppress inflammasome activation by interfering with host autophagy signaling.
Bacterial pathogens utilize pore-forming toxins or sophisticated secretion systems to establish infection in hosts. Recognition of these toxins or secretion system by nucleotide-binding oligomerization domain leucine-rich repeat proteins (NLRs) triggers the assembly of inflammasomes, the multiprotein complexes necessary for caspase-1 activation and the maturation of inflammatory cytokines such as IL-1β or IL-18. Here we demonstrate 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. Furthermore, we identify T3SS1 secreted effector proteins, VopQ and VopS, which induce autophagy and the inactivation of Cdc42, respectively, to prevent mainly NLRC4 inflammasome activation. VopQ and VopS interfere with the assembly of specks in infected macrophages. These data suggest that bacterial effectors interfere with inflammasome activation and contribute to bacterial evasion from the host inflammatory responses.
Department of Molecular Bacteriology and Immunology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
Naomi
N
Higa
Claudia
C
Toma
Yukiko
Y
Koizumi
Noboru
N
Nakasone
Toshitsugu
T
Nohara
Junya
J
Masumoto
Toshio
T
Kodama
Tetsuya
T
Iida
Toshihiko
T
Suzuki
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000276:immunology; D001427:Bacterial Toxins / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors; D006460:Hemolysin Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology*; D057131:Immune Evasion / Q000276:immunology; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012097:Repressor Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D014735:Vibrio Infections / Q000276:immunology* / Q000378:metabolism; D014736:Vibrio parahaemolyticus / Q000276:immunology / Q000472:pathogenicity*
D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D001427:Bacterial Toxins; D002352:Carrier Proteins; D016207:Cytokines; D004791:Enzyme Inhibitors; D006460:Hemolysin Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C466775:NLRP4 protein, human; D012097:Repressor Proteins; C068489:thermostable direct hemolysin