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RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection

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  • Amy E. L. Stone

    (University of Washington
    Touro University Nevada)

  • Richard Green

    (University of Washington)

  • Courtney Wilkins

    (University of Washington)

  • Emily A. Hemann

    (University of Washington)

  • Michael Gale

    (University of Washington)

Abstract

RIG-I-Like Receptors (RLRs) RIG-I, MDA5, and LGP2, are vital pathogen recognition receptors in the defense against RNA viruses. West Nile Virus (WNV) infections continue to grow in the US. Here, we use a systems biology approach to define the contributions of each RLR in the innate immune response to WNV. Genome-wide RNAseq and bioinformatics analyses of macrophages from mice lacking either RLR reveal that the RLRs drive distinct immune gene activation and response polarization to mediate an M1/inflammatory signature while suppressing the M2/wound healing phenotype. While LGP2 functions to modulate inflammatory signaling, RIG-I and MDA5 together are essential for M1 macrophage polarization in vivo and the control of WNV infection through potential downstream control of ATF4 and SMAD4 to regulate target gene expression for cell polarization. These analyses reveal the RLR-driven signature of macrophage polarization, innate immune protection, and immune programming against WNV infection.

Suggested Citation

  • Amy E. L. Stone & Richard Green & Courtney Wilkins & Emily A. Hemann & Michael Gale, 2019. "RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11250-5
    DOI: 10.1038/s41467-019-11250-5
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