AUTHOR=Luukkainen Annika , Puan Kia Joo , Yusof Nurhashikin , Lee Bernett , Tan Kai Sen , Liu Jing , Yan Yan , Toppila-Salmi Sanna , Renkonen Risto , Chow Vincent T. , Rotzschke Olaf , 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/journals/immunology/articles/10.3389/fimmu.2018.02514

DOI=10.3389/fimmu.2018.02514

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> We established an <italic>in vitro</italic> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusions:</bold> This system may contribute to <italic>in vitro</italic> mechanistic immunological studies bridging systemic models and possibly enable the development of targeted immunomodulatory therapies.</p>