Signal transducer and activator of transcription 4 (STAT4), but not IL-12 contributes to Pseudomonas aeruginosa-induced lung inflammation in mice.
Pseudomonas aeruginosa is a major opportunistic pathogen in immune-compromised individuals and cystic fibrosis patients. This organism stimulates a complex inflammatory response in the lung, including production of various cytokines and chemokines. The specific contribution of these mediators in the host defense against this bacterium has yet to be fully characterized. Interleukin-12 (IL-12) is commonly known as a master regulator of innate and adaptive immunity. IL-12 induces its biological effects through its associated intracellular signaling molecule, the signal transducer and activator of transcription 4 (STAT4). To examine a specific role of IL-12 and STAT4 in P. aeruginosa lung infection in mice, STAT4-deficient (STAT4-/-) and IL-12 p40-deficient (IL-12 p40-/-) mice were infected with P. aeruginosa intranasally. Interestingly, STAT4-/- mice, but not IL-12 p40-/- mice after 24h infection showed impaired production of the pro-inflammatory cytokines tumor necrosis factor, interleukin-1beta, and macrophage-inflammatory protein-2. However, neither STAT4 nor IL-12 p40 deficiency significantly affected INFgamma production or bacterial clearance compared to wild-type mice. Similarly, neutrophil recruitment was not affected in the STAT4-/- and IL-12 p40-/- mice. These results suggest that STAT4 contributes to P. aeruginosa-induced inflammation, but it is not essential for bacterial clearance. Although IL-12 is essential for the host defense against various pathogens, this cytokine is likely not a major player in the host response to P. aeruginosa lung infection.
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada B3K 6R8.
Rory
R
O'Sullivan
Svetlana O
SO
Carrigan
Jean S
JS
Marshall
Tong-Jun
TJ
Lin
D000818:Animals; D054426:Chemokine CXCL2 / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D007375:Interleukin-1; D050797:STAT4 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12