TY - JOUR
T1 - A role of Toll-IL-1 receptor domain-containing adaptor-inducing IFN-β in the host response to Pseudomonas aeruginosa lung infection in mice
AU - Power, Melanie R.
AU - Li, Bo
AU - Yamamoto, Masahiro
AU - Akira, Shizuo
AU - Lin, Tong Jun
PY - 2007/3/1
Y1 - 2007/3/1
N2 - Toll-IL-1R domain-containing adaptor-inducing IFN-β (TRIF) is an adaptor moiecnle 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-αβ. 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-κB 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-1β 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 prodection is completely dependent on TRIF pathway in mice. Importantly, TRIF deficiency leads to impaired clearance of P. aeruginosa from the long 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.
AB - Toll-IL-1R domain-containing adaptor-inducing IFN-β (TRIF) is an adaptor moiecnle 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-αβ. 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-κB 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-1β 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 prodection is completely dependent on TRIF pathway in mice. Importantly, TRIF deficiency leads to impaired clearance of P. aeruginosa from the long 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.
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U2 - 10.4049/jimmunol.178.5.3170
DO - 10.4049/jimmunol.178.5.3170
M3 - Article
C2 - 17312165
AN - SCOPUS:33847358354
SN - 0022-1767
VL - 178
SP - 3170
EP - 3176
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -