Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome.
Pseudomonas aeruginosa is a Gram-negative bacterium that causes opportunistic infections in immunocompromised individuals. P. aeruginosa employs a type III secretion system to inject effector molecules into the cytoplasm of the host cell. This interaction with the host cell leads to inflammatory responses that eventually result in cell death. We show that infection of macrophages with P. aeruginosa results in activation of caspase-1 in an IPAF-dependent, but flagellin-independent, manner. Macrophages deficient in IPAF or caspase-1 were markedly resistant to P. aeruginosa-induced cell death and release of the proinflammatory cytokine interleukin (IL)-1beta. A subset of P. aeruginosa isolates express the effector molecule exoenzyme U (ExoU), which we demonstrate is capable of inhibiting caspase-1-driven proinflammatory cytokine production. This study shows a key role for IPAF and capase-1 in innate immune responses to the pathogen P. aeruginosa, and also demonstrates that virulent ExoU-expressing strains of P. aeruginosa can circumvent this innate immune response.
Sutterwala
Fayyaz S
FS
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Mijares
Lilia A
LA
Li
Li
L
Ogura
Yasunori
Y
Kazmierczak
Barbara I
BI
Flavell
Richard A
RA
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D016923:Cell Death; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D005408:Flagellin / Q000378:metabolism; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; D005408:Flagellin; D020170:Caspase 1