| First Author | Seki M | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 3 | Pages | 1410-8 |
| PubMed ID | 20042589 | Mgi Jnum | J:159499 |
| Mgi Id | MGI:4443179 | Doi | 10.4049/jimmunol.0901709 |
| Citation | Seki M, et al. (2010) Critical role of IL-1 receptor-associated kinase-M in regulating chemokine-dependent deleterious inflammation in murine influenza pneumonia. J Immunol 184(3):1410-8 |
| abstractText | Influenza virus is a common cause of respiratory infection and morbidity, which is often due to deleterious host immune responses directed against the pathogen. We investigated the role of IL-1 receptor-associated kinase-M (IRAK-M), an inhibitor of MyD88-dependent TLR signaling, in modulating the innate inflammatory response during influenza pneumonia using a murine model. The intranasal administration of influenza resulted in the upregulation of IRAK-M mRNA and protein levels in the lungs within 2 d after infectious challenge. Pulmonary influenza infection in mice deficient in IRAK-M (IRAK-M(-/-)) resulted in substantially increased mortality compared with similarly treated wild-type animals. Increased mortality in IRAK-M(-/-) mice was associated with enhanced early influx of neutrophils, high permeability edema, apoptosis of lung epithelial cells, markedly increased expression of inflammatory cytokines/chemokines, and release of neutrophil-derived enzymes, including myeloperoxidase and neutrophil elastase. Early viral clearance was not different in mutant mice, whereas viral titers in lungs and blood were significantly higher in IRAK-M(-/-) mice compared with wild-type animals. Increased lethality observed in IRAK-M(-/-) mice after influenza challenge was abrogated by Ab-mediated blockade of CXCR2. Collectively, our findings indicate that IRAK-M is critical to preventing deleterious neutrophil-dependent lung injury during influenza infection of the respiratory tract. |
