{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:13:06Z","timestamp":1788408786205,"version":"build-2803163510"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Influenza viruses lead to substantial morbidity and mortality including ~3-5 million cases of severe illness and ~290,000-650,000 deaths annually. One of the major hurdles regarding influenza vaccine efficacy is generating a durable, robust cellular immune response. Appropriate stimulation of the innate immune system is key to generating cellular immunity. Cross-talk between innate dendritic cells (DC) and natural killer (NK) cells plays a key role in activating virus-specific T cells, yet the mechanisms used by influenza A viruses (IAV) to govern this process remain incompletely understood. Here, we used an<jats:italic>ex vivo<\/jats:italic>autologous human primary immune cell culture system to evaluate the impact of DC-NK cell cross-talk and subsequent na\u00efve T cell activation at steady-state and after exposure to genetically distinct IAV strains\u2013A\/California\/07\/2009 (H1N1) and A\/Victoria\/361\/2011 (H3N2). Using flow cytometry, we found that exposure of DCs to IAV in co-culture with NK cells led to a decreased frequency of CD83<jats:sup>+<\/jats:sup>and CD86<jats:sup>+<\/jats:sup>cells on DCs and an increased frequency of HLA-DR<jats:sup>+<\/jats:sup>on both DCs and NK cells. We then assessed the outcome of DC-NK cell cross-talk on T cell activation. At steady-state, DC-NK cell cross-talk increased pan T cell CD69 and CD25 expression while exposure to either IAV strain reduced pan T cell CD25 expression and suppressed CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cell IFN-\u03b3 and TNF production, following chemical stimulation with PMA\/Ionomycin. Moreover, exposure to A\/Victoria\/361\/2011 elicited lower IFN-\u03b3 production by CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells compared with A\/California\/07\/2009. Overall, our results indicate a role for DC-NK cell cross-talk in T cell priming in the context of influenza infection, informing the immunological mechanisms that could be manipulated for the next generation of influenza vaccines or immunotherapeutics.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1006998","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T12:06:11Z","timestamp":1671710771000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Dendritic cell-natural killer cell cross-talk modulates T cell activation in response to influenza A viral infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Abigail G.","family":"Harvey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athens M.","family":"Graves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandana 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