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

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 t...

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Autores principales: Stone, Amy E. L., Green, Richard, Wilkins, Courtney, Hemann, Emily A., Gale, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692387/
https://www.ncbi.nlm.nih.gov/pubmed/31409781
http://dx.doi.org/10.1038/s41467-019-11250-5
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author Stone, Amy E. L.
Green, Richard
Wilkins, Courtney
Hemann, Emily A.
Gale, Michael
author_facet Stone, Amy E. L.
Green, Richard
Wilkins, Courtney
Hemann, Emily A.
Gale, Michael
author_sort Stone, Amy E. L.
collection PubMed
description 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.
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spelling pubmed-66923872019-08-15 RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection Stone, Amy E. L. Green, Richard Wilkins, Courtney Hemann, Emily A. Gale, Michael Nat Commun Article 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. Nature Publishing Group UK 2019-08-13 /pmc/articles/PMC6692387/ /pubmed/31409781 http://dx.doi.org/10.1038/s41467-019-11250-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Stone, Amy E. L.
Green, Richard
Wilkins, Courtney
Hemann, Emily A.
Gale, Michael
RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection
title RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection
title_full RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection
title_fullStr RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection
title_full_unstemmed RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection
title_short RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection
title_sort rig-i-like receptors direct inflammatory macrophage polarization against west nile virus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692387/
https://www.ncbi.nlm.nih.gov/pubmed/31409781
http://dx.doi.org/10.1038/s41467-019-11250-5
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