| First Author | Kuriakose T | Year | 2015 |
| Journal | PLoS Pathog | Volume | 11 |
| Issue | 8 | Pages | e1005038 |
| PubMed ID | 26241898 | Mgi Jnum | J:247226 |
| Mgi Id | MGI:5917930 | Doi | 10.1371/journal.ppat.1005038 |
| Citation | Kuriakose T, et al. (2015) Tumor Progression Locus 2 Promotes Induction of IFNlambda, Interferon Stimulated Genes and Antigen-Specific CD8+ T Cell Responses and Protects against Influenza Virus. PLoS Pathog 11(8):e1005038 |
| abstractText | Mitogen-activated protein kinase (MAP) cascades are important in antiviral immunity through their regulation of interferon (IFN) production as well as virus replication. Although the serine-threonine MAP kinase tumor progression locus 2 (Tpl2/MAP3K8) has been implicated as a key regulator of Type I (IFNalpha/beta) and Type II (IFNgamma) IFNs, remarkably little is known about how Tpl2 might contribute to host defense against viruses. Herein, we investigated the role of Tpl2 in antiviral immune responses against influenza virus. We demonstrate that Tpl2 is an integral component of multiple virus sensing pathways, differentially regulating the induction of IFNalpha/beta and IFNlambda in a cell-type specific manner. Although Tpl2 is important in the regulation of both IFNalpha/beta and IFNlambda, only IFNlambda required Tpl2 for its induction during influenza virus infection both in vitro and in vivo. Further studies revealed an unanticipated function for Tpl2 in transducing Type I IFN signals and promoting expression of interferon-stimulated genes (ISGs). Importantly, Tpl2 signaling in nonhematopoietic cells is necessary to limit early virus replication. In addition to early innate alterations, impaired expansion of virus-specific CD8+ T cells accompanied delayed viral clearance in Tpl2-/- mice at late time points. Consistent with its critical role in facilitating both innate and adaptive antiviral responses, Tpl2 is required for restricting morbidity and mortality associated with influenza virus infection. Collectively, these findings establish an essential role for Tpl2 in antiviral host defense mechanisms. |
