Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7
The innate immune system senses influenza A virus (IAV) through different pathogen-recognition receptors including Toll-like receptor 7 (TLR7). Downstream of viral recognition natural killer (NK) cells are activated as part of the anti-IAV immune response. Despite the known decisive role of TLR7 for...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00245/full |
| _version_ | 1819260781350354944 |
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| author | Sabine Stegemann-Koniszewski Sabine Stegemann-Koniszewski Sabine Stegemann-Koniszewski Sarah Behrens Julia D. Boehme Julia D. Boehme Inga Hochnadel Peggy Riese Carlos A. Guzmán Andrea Kröger Andrea Kröger Jens Schreiber Matthias Gunzer Dunja Bruder Dunja Bruder |
| author_facet | Sabine Stegemann-Koniszewski Sabine Stegemann-Koniszewski Sabine Stegemann-Koniszewski Sarah Behrens Julia D. Boehme Julia D. Boehme Inga Hochnadel Peggy Riese Carlos A. Guzmán Andrea Kröger Andrea Kröger Jens Schreiber Matthias Gunzer Dunja Bruder Dunja Bruder |
| author_sort | Sabine Stegemann-Koniszewski |
| collection | DOAJ |
| description | The innate immune system senses influenza A virus (IAV) through different pathogen-recognition receptors including Toll-like receptor 7 (TLR7). Downstream of viral recognition natural killer (NK) cells are activated as part of the anti-IAV immune response. Despite the known decisive role of TLR7 for NK cell activation by therapeutic immunostimulatory RNAs, the contribution of TLR7 to the NK cell response following IAV infection has not been addressed. We have analyzed lung cytokine responses as well as the activation, interferon (IFN)-γ production, and cytotoxicity of lung and splenic NK cells following sublethal respiratory IAV infection in wild-type and TLR7ko mice. Early airway IFN-γ levels as well as the induction of lung NK cell CD69 expression and IFN-γ production in response to IAV infection were significantly attenuated in TLR7-deficient hosts. Strikingly, respiratory IAV infection also primed splenic NK cells for IFN-γ production, degranulation, and target cell lysis, all of which were fully dependent on TLR7. At the same time, lung type I IFN levels were significantly reduced in TLR7ko mice early following IAV infection, displaying a potential upstream mechanism of the attenuated NK cell activation observed. Taken together, our data clearly demonstrate a specific role for TLR7 signaling in local and systemic NK cell activation following respiratory IAV infection despite the presence of redundant innate IAV-recognition pathways. |
| first_indexed | 2024-12-23T19:31:22Z |
| format | Article |
| id | doaj.art-475ebca8b90a4906a4af9684513b1692 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T19:31:22Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-475ebca8b90a4906a4af9684513b16922022-12-21T17:33:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01910.3389/fimmu.2018.00245312113Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7Sabine Stegemann-Koniszewski0Sabine Stegemann-Koniszewski1Sabine Stegemann-Koniszewski2Sarah Behrens3Julia D. Boehme4Julia D. Boehme5Inga Hochnadel6Peggy Riese7Carlos A. Guzmán8Andrea Kröger9Andrea Kröger10Jens Schreiber11Matthias Gunzer12Dunja Bruder13Dunja Bruder14Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, GermanyInfection Immunology, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto von-Guericke University, Magdeburg, GermanyExperimental Pneumology, University Hospital of Pneumology, University Hospital Magdeburg, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, Magdeburg, GermanyImmune Regulation, Helmholtz Centre for Infection Research, Braunschweig, GermanyImmune Regulation, Helmholtz Centre for Infection Research, Braunschweig, GermanyInfection Immunology, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto von-Guericke University, Magdeburg, GermanyImmune Regulation, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, GermanyMolecular Microbiology, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, Magdeburg, GermanyInnate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig, GermanyExperimental Pneumology, University Hospital of Pneumology, University Hospital Magdeburg, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, Magdeburg, GermanyInstitute for Experimental Immunology and Imaging, University Hospital, University of Duisburg-Essen, Essen, GermanyImmune Regulation, Helmholtz Centre for Infection Research, Braunschweig, GermanyInfection Immunology, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto von-Guericke University, Magdeburg, GermanyThe innate immune system senses influenza A virus (IAV) through different pathogen-recognition receptors including Toll-like receptor 7 (TLR7). Downstream of viral recognition natural killer (NK) cells are activated as part of the anti-IAV immune response. Despite the known decisive role of TLR7 for NK cell activation by therapeutic immunostimulatory RNAs, the contribution of TLR7 to the NK cell response following IAV infection has not been addressed. We have analyzed lung cytokine responses as well as the activation, interferon (IFN)-γ production, and cytotoxicity of lung and splenic NK cells following sublethal respiratory IAV infection in wild-type and TLR7ko mice. Early airway IFN-γ levels as well as the induction of lung NK cell CD69 expression and IFN-γ production in response to IAV infection were significantly attenuated in TLR7-deficient hosts. Strikingly, respiratory IAV infection also primed splenic NK cells for IFN-γ production, degranulation, and target cell lysis, all of which were fully dependent on TLR7. At the same time, lung type I IFN levels were significantly reduced in TLR7ko mice early following IAV infection, displaying a potential upstream mechanism of the attenuated NK cell activation observed. Taken together, our data clearly demonstrate a specific role for TLR7 signaling in local and systemic NK cell activation following respiratory IAV infection despite the presence of redundant innate IAV-recognition pathways.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00245/fullinfluenza A virusnatural killer cellspathogen-recognition receptorsToll-like receptor 7innate immunityrespiratory infection |
| spellingShingle | Sabine Stegemann-Koniszewski Sabine Stegemann-Koniszewski Sabine Stegemann-Koniszewski Sarah Behrens Julia D. Boehme Julia D. Boehme Inga Hochnadel Peggy Riese Carlos A. Guzmán Andrea Kröger Andrea Kröger Jens Schreiber Matthias Gunzer Dunja Bruder Dunja Bruder Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7 Frontiers in Immunology influenza A virus natural killer cells pathogen-recognition receptors Toll-like receptor 7 innate immunity respiratory infection |
| title | Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7 |
| title_full | Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7 |
| title_fullStr | Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7 |
| title_full_unstemmed | Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7 |
| title_short | Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7 |
| title_sort | respiratory influenza a virus infection triggers local and systemic natural killer cell activation via toll like receptor 7 |
| topic | influenza A virus natural killer cells pathogen-recognition receptors Toll-like receptor 7 innate immunity respiratory infection |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00245/full |
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