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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 Infec

tetano

Editor, Senior Moderator
Front Immunol. 2018 Nov 8;9:2514. doi: 10.3389/fimmu.2018.02514. eCollection 2018.
[h=1]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.[/h] Luukkainen A[SUP]1,[/SUP][SUP]2[/SUP], Puan KJ[SUP]3[/SUP], Yusof N[SUP]3[/SUP], Lee B[SUP]3[/SUP], Tan KS[SUP]1[/SUP], Liu J[SUP]1[/SUP], Yan Y[SUP]1[/SUP], Toppila-Salmi S[SUP]2,[/SUP][SUP]4[/SUP], Renkonen R[SUP]2,[/SUP][SUP]5[/SUP], Chow VT[SUP]6[/SUP], Rotzschke O[SUP]3[/SUP], Wang Y[SUP]1[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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.


[h=4]KEYWORDS:[/h] co-culture; influenza A virus; innate T cells; nasal epithelium; peripheral blood mononuclear cells

PMID: 30467502 PMCID: PMC6237251 DOI: 10.3389/fimmu.2018.02514
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