Article ; Online: Myeloid TBK1 Signaling Contributes to the Immune Response to Influenza.
American journal of respiratory cell and molecular biology
2018 Volume 60, Issue 3, Page(s) 335–345
Abstract: ... consequences of IAV infection. Myeloid-specific loss of TBK1 in vivo resulted in less severe host response ... We hypothesized that macrophage TBK1 contributes to both IFN and non-IFN components of host defense and IAV ... Macrophages provide key elements of the host response to influenza A virus (IAV) infection ...
| Abstract | Macrophages provide key elements of the host response to influenza A virus (IAV) infection, including expression of type I IFN and inflammatory cytokines and chemokines. TBK1 (TNF receptor-associated factor family member-associated NF-κB activator-binding kinase 1) contributes to IFN expression and antiviral responses in some cell types, but its role in the innate response to IAV in vivo is unknown. We hypothesized that macrophage TBK1 contributes to both IFN and non-IFN components of host defense and IAV pathology. We generated myeloid-conditional TBK1 knockout mice and assessed the in vitro and in vivo consequences of IAV infection. Myeloid-specific loss of TBK1 in vivo resulted in less severe host response to IAV, as assessed by decreased mortality, weight loss, and hypoxia and less inflammatory changes in BAL fluid relative to wild-type mice despite no differences in viral load. Mice lacking myeloid TBK1 showed less recruitment of CD64 |
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| MeSH term(s) | Animals ; Cytokines/immunology ; Influenza A Virus, H1N1 Subtype/immunology ; Lung/immunology ; Macrophages, Alveolar/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Cells/immunology ; NF-kappa B/immunology ; Orthomyxoviridae Infections/immunology ; Pneumonia/metabolism ; Protein-Serine-Threonine Kinases/immunology ; Signal Transduction/immunology | |||||
| Chemical Substances | Cytokines ; NF-kappa B ; Tbk1 protein, mouse (EC 2.7.1.-) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) | |||||
| Language | English | |||||
| Publishing date | 2018-10-04 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 1025960-0 | |||||
| ISSN | 1535-4989 ; 1044-1549 | |||||
| ISSN (online) | 1535-4989 | |||||
| ISSN | 1044-1549 | |||||
| DOI | 10.1165/rcmb.2018-0122OC | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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