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Tumor Progression Locus 2 Promotes Induction of IFNλ, Interferon Stimulated Genes and Antigen-Specific CD8 T Cell Responses and Protects against Influenza Virus


Influenza viruses infect millions of people annually causing significant morbidity, mortality and socio-economic burdens. Host immune responses against influenza virus are initiated upon virus recognition by specific intracellular receptors. Signals relayed from these receptors trigger various signaling cascades, which induce an antiviral immune response to control infection. Herein, we identified the serine-threonine kinase tumor progression locus 2 (Tpl2) as an essential component of virus sensing pathways, regulating induction of interferons (IFNs) and IFN-induced antiviral genes that restrict virus replication. We also demonstrate that Tpl2 is necessary for generation of effector CD8+ T cells, which are required for viral clearance from infected lungs. Consistent with the impaired antiviral responses, Tpl2-deficient mice are defective in controlling virus replication and succumb to influenza virus infection with a normally low pathogenicity strain. Thus, our study identifies Tpl2 as a host factor that integrates antiviral innate and adaptive responses to restrict morbidity and mortality during influenza virus infection.


Vyšlo v časopise: Tumor Progression Locus 2 Promotes Induction of IFNλ, Interferon Stimulated Genes and Antigen-Specific CD8 T Cell Responses and Protects against Influenza Virus. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005038
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005038

Souhrn

Influenza viruses infect millions of people annually causing significant morbidity, mortality and socio-economic burdens. Host immune responses against influenza virus are initiated upon virus recognition by specific intracellular receptors. Signals relayed from these receptors trigger various signaling cascades, which induce an antiviral immune response to control infection. Herein, we identified the serine-threonine kinase tumor progression locus 2 (Tpl2) as an essential component of virus sensing pathways, regulating induction of interferons (IFNs) and IFN-induced antiviral genes that restrict virus replication. We also demonstrate that Tpl2 is necessary for generation of effector CD8+ T cells, which are required for viral clearance from infected lungs. Consistent with the impaired antiviral responses, Tpl2-deficient mice are defective in controlling virus replication and succumb to influenza virus infection with a normally low pathogenicity strain. Thus, our study identifies Tpl2 as a host factor that integrates antiviral innate and adaptive responses to restrict morbidity and mortality during influenza virus infection.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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