@ARTICLE{10.3389/fimmu.2018.02514, AUTHOR={Luukkainen, Annika and Puan, Kia Joo and Yusof, Nurhashikin and Lee, Bernett and Tan, Kai Sen and Liu, Jing and Yan, Yan and Toppila-Salmi, Sanna and Renkonen, Risto and Chow, Vincent T. and Rotzschke, Olaf and Wang, De Yun}, TITLE={A Co-culture Model of PBMC and Stem Cell Derived Human Nasal Epithelium Reveals Rapid Activation of NK and Innate T Cells Upon Influenza A Virus Infection of the Nasal Epithelium}, JOURNAL={Frontiers in Immunology}, VOLUME={9}, YEAR={2018}, URL={https://www.frontiersin.org/articles/10.3389/fimmu.2018.02514}, DOI={10.3389/fimmu.2018.02514}, ISSN={1664-3224}, ABSTRACT={Background: We established an in vitro co-culture model involving H3N2-infection of human nasal epithelium with peripheral blood mononuclear cells (PBMC) to investigate their cross-talk during early H3N2 infection.Methods: Nasal epithelium was differentiated from human nasal epithelial stem/progenitor cells and cultured wtih fresh human PBMC. PBMC and supernatants were harvested after 24 and 48 h of co-culture with H3N2-infected nasal epithelium. We used flow cytometry and Luminex to characterize PBMC subpopulations, their activation and secretion of cytokine and chemokines.Results: H3N2 infection of the nasal epithelium associated with significant increase in interferons (IFN-α, IFN-γ, IL-29), pro-inflammatory cytokines (TNF-α, BDNF, IL-3) and viral-associated chemokines (IP-10, MCP-3, I-TAC, MIG), detectable already after 24 h. This translates into rapid activation of monocytes, NK-cells and innate T-cells (MAIT and γδ T cells), evident with CD38+ and/or CD69+ upregulation.Conclusions: This system may contribute to in vitro mechanistic immunological studies bridging systemic models and possibly enable the development of targeted immunomodulatory therapies.} }