A role of Toll-IL-1 receptor domain-containing adaptor-inducing IFN-beta in the host response to Pseudomonas aeruginosa lung infection in mice.
Toll-IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) is an adaptor molecule that mediates a distinct TLR signaling pathway. Roles of TRIF in the host defense have been primarily associated with virus infections owing to the induction of IFN-alphabeta. In this study, we investigated a role of TRIF in Pseudomonas aeruginosa infection. In vitro, TRIF-deficient mouse alveolar and peritoneal macrophages showed a complete inhibition of RANTES (CCL5) production, severely impaired TNF and KC (CXCL1) production, and reduced NF-kappaB activation in response to P. aeruginosa stimulation. In vivo, TRIF-deficient mice showed a complete inhibition of RANTES production, a severely impaired TNF and KC production, and an efficient MIP-2 and IL-1beta production in the lung following P. aeruginosa infection. This outcome was associated with a delayed recruitment of neutrophils into the airways. These results suggest that TRIF mediates a distinct cytokine/chemokine profile in response to P. aeruginosa infection. P. aeruginosa-induced RANTES production is completely dependent on TRIF pathway in mice. Importantly, TRIF deficiency leads to impaired clearance of P. aeruginosa from the lung during the initial 24-48 h of infection. Thus, TRIF represents a novel mechanism involved in the development of host response to P. aeruginosa infection.
Power
Melanie R
MR
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Li
Bo
B
Yamamoto
Masahiro
M
Akira
Shizuo
S
Lin
Tong-Jun
TJ
D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D013997:Time Factors
D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D016899:Interferon-beta; D016328:NF-kappa B; C476286:Ticam1 protein, mouse