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Visualizing the Selectivity and Dynamics of Interferon Signaling In Vivo

  1. Author:
    Stifter, Sebastian A.
    Bhattacharyya, Nayan
    Sawyer, Andrew J.
    Cootes, Taylor A.
    Stambas, John
    Doyle, Sean E.
    Feigenbaum, Lionel
    Paul, William E.
    Britton, Warwick J.
    Sher, Alan
    Feng, Carl G.

  2. Author Address

    Univ Sydney, Fac Med & Hlth, Discipline Infect Dis & Immunol, Immunol & Host Def Grp, Sydney, NSW 2006, Australia.Univ Sydney, Centenary Inst, Sydney, NSW 2050, Australia.Deakin Univ, Sch Med, Geelong, Vic 3216, Australia.Bristol Myers Squibb, Seattle, WA 98102 USA.NCI, Lab Anim Sci Program, Frederick, MD 21702 USA.NIAID, Cytokine Biol Unit, Lab Immunol, NIH, Bethesda, MD 20892 USA.Univ Sydney, Fac Med & Hlth, Cent Clin Sch, Sydney, NSW 2006, Australia.NIAID, Immunobiol Sect, Lab Parasit Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.Univ Zurich, Inst Expt Immunol, CH-8057 Zurich, Switzerland.
    1. Year: 2019
    2. Date: Dec 10
  2. Journal: Cell reports
  3. CELL PRESS,
    1. 29
    2. 11
    3. Pages: 3539-3550.e4
  5. Type of Article: Article
  6. ISSN: 2211-1247
  1. Abstract:

    Interferons (IFN) are pleiotropic cytokines essential for defense against infection, but the identity and tissue distribution of IFN-responsive cells in vivo are poorly defined. In this study, we generate a mouse strain capable of reporting IFN-signaling activated by all three types of IFNs and investigate the spatio-temporal dynamics and identity of IFN-responding cells following IFN injection and influenza virus infection. Despite ubiquitous expression of IFN receptors, cellular responses to IFNs are highly heterogenous in vivo and are determined by anatomical site, cell type, cellular preference to individual IFNs, and activation status. Unexpectedly, type I and II pneumocytes, the primary target of influenza infection, exhibit striking differences in the strength and temporal dynamics of IFN signaling associated with differential susceptibility to the viral infection. Our findings suggest that time- and cell-type-dependent integration of distinct IFN signals govern the specificity and magnitude of IFN responses in vivo.

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External Sources

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  2. DOI: 10.1016/j.celrep.2019.11.021
  3. PMID: 31825834
  4. View record in Web of Science®
  5. WOS: 000502113400016

Library Notes

  1. Fiscal Year: FY2019-2020
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