CCR5 is a required signaling receptor for macrophage expression of inflammatory genes in response to viral double-stranded RNA

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Zachary R ShaheenJohn A Corbett

Abstract

Double-stranded (ds) RNA, both synthetic and produced during virus replication, rapidly stimulates MAPK and NF-κB signaling that results in expression of the inflammatory genes inducible nitric oxide synthase, cyclooxygenase 2, and IL-1β by macrophages. Using biochemical and genetic approaches, we have identified the chemokine ligand-binding C-C chemokine receptor type 5 (CCR5) as a cell surface signaling receptor required for macrophage expression of inflammatory genes in response to dsRNA. Activation of macrophages by synthetic dsRNA does not require known dsRNA receptors, as poly(inosinic:cytidylic) acid [poly(I:C)] activates signaling pathways leading to expression of inflammatory genes to similar levels in wild-type and Toll-like receptor 3- or melanoma differentiation antigen 5-deficient macrophages. In contrast, macrophage activation in response to poly(I:C) is attenuated in macrophages isolated from mice lacking CCR5. These findings support a role for CCR5 as a cell surface signaling receptor that participates in activation of inflammatory genes in macrophages in response to the viral dsRNA mimetic poly(inosinic:cytidylic) acid by pathways that are distinct from classical dsRNA receptor-mediated responses.

References

Oct 28, 1988·Science·P A Baeuerle, D Baltimore
Oct 1, 1982·Analytical Biochemistry·L C GreenS R Tannenbaum
Jun 1, 1993·Current Opinion in Cell Biology·H C Liou, D Baltimore
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·R J Kaufman
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·M C YeungA S Lau
Jul 19, 2000·The EMBO Journal·L B MaggiJ A Corbett
Jan 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Dong-chul KangPaul B Fisher
Oct 3, 2002·Nature Reviews. Drug Discovery·Susan R GeorgeSamuel P Lee
Jan 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah A SteerJohn A Corbett
Mar 1, 2003·The Journal of Biological Chemistry·Leonard B MaggiJohn A Corbett
Sep 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Misako MatsumotoTsukasa Seya
Sep 1, 2004·Cellular Signalling·Martin Oppermann
Nov 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·J AndrejevaR E Randall
Feb 16, 2005·Nature·Oliver SchulzCaetano Reis e Sousa
May 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Leonid GitlinMarco Colonna
Jun 10, 2006·Molecular Cell·Etienne Meylan, Jürg Tschopp
Jul 22, 2006·The EMBO Journal·Ingvild Bjellmo JohnsenMarit W Anthonsen
Aug 15, 2006·JAMA : the Journal of the American Medical Association·Michael M LedermanDonald Mosier
Aug 16, 2006·European Journal of Immunology·Trevor WhittallThomas Lehner
Aug 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah A SteerJohn A Corbett
Sep 19, 2006·Immunity·Daniel B Stetson, Ruslan Medzhitov
Oct 21, 2006·Science·R Andres FlotoPaul J Lehner
Feb 13, 2007·Annual Review of Immunology·Samantha J AllenTracy M Handel

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Citations

Jan 10, 2020·The Journal of Biological Chemistry·Zachary R ShaheenJohn A Corbett
Feb 13, 2020·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Willis K Samson
Jan 30, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Luciana P TavaresRemo C Russo
May 7, 2020·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Gina L C Yosten
Jun 3, 2021·International Journal of Molecular Sciences·Sueva CantalupoMario Capasso
Aug 13, 2021·Nature Communications·Geraldine NouaillesMartin Witzenrath
Nov 7, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Duale AhmedEdana Cassol

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Methods Mentioned

BETA
nucleotide exchange
PCR
ELISA
PECs
electrophoresis
surface plasmon resonance

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