| First Author | Demoor T | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 12 | Pages | 5942-53 |
| PubMed ID | 23136205 | Mgi Jnum | J:190876 |
| Mgi Id | MGI:5449818 | Doi | 10.4049/jimmunol.1201763 |
| Citation | Demoor T, et al. (2012) IPS-1 Signaling Has a Nonredundant Role in Mediating Antiviral Responses and the Clearance of Respiratory Syncytial Virus. J Immunol 189(12):5942-53 |
| abstractText | The cytosolic RNA helicases melanoma differentiation-associated gene 5 and retinoic acid-inducible gene-I and their adaptor IFN-beta promoter stimulator (IPS-1) have been implicated in the recognition of viral RNA and the production of type I IFN. Complementing the endosomal TLR, melanoma differentiation-associated gene 5, and retinoic acid-inducible gene-I provides alternative mechanisms for viral detection in cells with reduced phagocytosis or autophagy. The infection route of respiratory syncytial virus (RSV)-via fusion of virus particles with the cell membrane-points to IPS-1 signaling as the pathway of choice for downstream antiviral responses. In the current study, viral clearance and inflammation resolution were indeed strongly affected by the absence of an initial IPS-1-mediated IFN-beta response. Despite the blunted inflammatory response in IPS-1-deficient alveolar epithelial cells, pulmonary macrophages, and CD11b(+) dendritic cells (DC), the lungs of RSV-infected IPS-1-knockout mice showed augmented recruitment of inflammatory neutrophils, monocytes, and DC. Interestingly, pulmonary CD103(+) DC could functionally compensate for IPS-1 deficiency with the upregulation of certain inflammatory cytokines and chemokines, possibly via TLR3 and TLR7 signaling. The increased inflammation and reduced viral clearance in IPS-1-knockout mice was accompanied by increased T cell activation and IFN-gamma production. Experiments with bone marrow chimeras indicated that RSV-induced lung pathology was most severe when IPS-1 expression was lacking in both immune and nonimmune cell populations. Similarly, viral clearance was rescued upon restored IPS-1 signaling in either the nonimmune or the immune compartment. These data support a nonredundant function for IPS-1 in controlling RSV-induced inflammation and viral replication. |
