CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection

Jeffrey Tyner, Osamu Uchida, Naohiro Kajiwara, Edy Y. Kim, Anand C. Patel, Mary P. O'Sullivan, Michael J. Walter, Reto A. Schwendener, Donald N. Cook, Theodore M. Danoff, Michael J. Holtzman

Research output: Contribution to journalArticle

189 Citations (Scopus)

Abstract

Host defense against viruses probably depends on targeted death of infected host cells and then clearance of cellular corpses by macrophages. For this process to be effective, the macrophage must presumably avoid its own virus-induced death. Here we identify one such mechanism. We show that mice lacking the chemokine Ccl5 are immune compromised to the point of delayed viral clearance, excessive airway inflammation and respiratory death after mouse parainfluenza or human influenza virus infection. Virus-inducible levels of Ccl5 are required to prevent apoptosis of virus-infected mouse macrophages in vivo and mouse and human macrophages ex vivo. The protective effect of Ccl5 requires activation of the Ccr5 chemokine receptor and consequent bilateral activation of Gαi-PI3K-AKT and Gαi-MEK-ERK signaling pathways. The antiapoptotic action of chemokine signaling may therefore allow scavengers to finally stop the host cell-to-cell infectious process.

Original languageEnglish (US)
Pages (from-to)1180-1187
Number of pages8
JournalNature Medicine
Volume11
Issue number11
DOIs
StatePublished - Nov 2005
Externally publishedYes

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Macrophages
Virus Diseases
Viruses
Chemokines
Paramyxoviridae Infections
Bridge clearances
Chemical activation
MAP Kinase Signaling System
Chemokine Receptors
Orthomyxoviridae
Phosphatidylinositol 3-Kinases
Cadaver
Human Influenza
Mitogen-Activated Protein Kinase Kinases
Apoptosis
Inflammation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tyner, J., Uchida, O., Kajiwara, N., Kim, E. Y., Patel, A. C., O'Sullivan, M. P., ... Holtzman, M. J. (2005). CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Nature Medicine, 11(11), 1180-1187. https://doi.org/10.1038/nm1303

CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. / Tyner, Jeffrey; Uchida, Osamu; Kajiwara, Naohiro; Kim, Edy Y.; Patel, Anand C.; O'Sullivan, Mary P.; Walter, Michael J.; Schwendener, Reto A.; Cook, Donald N.; Danoff, Theodore M.; Holtzman, Michael J.

In: Nature Medicine, Vol. 11, No. 11, 11.2005, p. 1180-1187.

Research output: Contribution to journalArticle

Tyner, J, Uchida, O, Kajiwara, N, Kim, EY, Patel, AC, O'Sullivan, MP, Walter, MJ, Schwendener, RA, Cook, DN, Danoff, TM & Holtzman, MJ 2005, 'CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection', Nature Medicine, vol. 11, no. 11, pp. 1180-1187. https://doi.org/10.1038/nm1303
Tyner, Jeffrey ; Uchida, Osamu ; Kajiwara, Naohiro ; Kim, Edy Y. ; Patel, Anand C. ; O'Sullivan, Mary P. ; Walter, Michael J. ; Schwendener, Reto A. ; Cook, Donald N. ; Danoff, Theodore M. ; Holtzman, Michael J. / CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. In: Nature Medicine. 2005 ; Vol. 11, No. 11. pp. 1180-1187.
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