Coordinate Expression of Cytokines and Chemokines by NK Cells during Murine Cytomegalovirus Infection

Brigitte G. Dorner, Hamish R.C. Smith, Anthony R. French, Sung Jin Kim, Jennifer Poursine-Laurent, Diana L. Beckman, Jeanette T. Pingel, Richard A. Kroczek, Wayne M. Yokoyama

Research output: Contribution to journalArticle

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Abstract

Cytokines and chemokines activate and direct effector cells during infection. We previously identified a functional group of five cytokines and chemokines, namely, IFN-γ, activation-induced T cell-derived and chemokine-related cytokine/lymphotactin, macrophage-inflammatory protein 1α, macrophage-inflammatory protein 1β, and RANTES, coexpressed in individual activated NK cells, CD8+ T cells, and CD4+ Th1 cells in vitro and during in vivo infections. However, the stimuli during infection were not known. In murine CMV (MCMV) infection, the DAP12/KARAP-associated Ly49H NK cell activation receptor is crucial for resistance through recognition of MCMV-encoded m157 but NK cells also undergo in vivo nonspecific responses to uncharacterized stimuli. In this study, we show that Ly49H ligation by m157 resulted in a coordinated release of all five cytokines/ chemokines from Ly49H+ NK cells. Whereas other cytokines also triggered the release of these cytokines/chemokines, stimulation was not confined to the Ly49H+ population. At the single-cell level, the production of the five mediators showed strong positive correlation with each other. Interestingly, NK cells were a major source of these five cytokines/chemokines in vitro and in vivo, whereas infected macrophages produced only limited amounts of macrophage-inflammatory protein 1α, macrophage-inflammatory protein1β, and RANTES. These findings suggest that both virus-specific and nonspecific NK cells play crucial roles in activating and directing other inflammatory cells during MCMV infection.

Original languageEnglish (US)
Pages (from-to)3119-3131
Number of pages13
JournalJournal of Immunology
Volume172
Issue number5
StatePublished - Mar 1 2004
Externally publishedYes

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Muromegalovirus
Cytomegalovirus Infections
Chemokines
Natural Killer Cells
Cytokines
Macrophage Inflammatory Proteins
Infection
Chemokine CCL5
Macrophages
Natural Killer Cell Receptors
T-Lymphocytes
Th1 Cells
Ligation
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Dorner, B. G., Smith, H. R. C., French, A. R., Kim, S. J., Poursine-Laurent, J., Beckman, D. L., ... Yokoyama, W. M. (2004). Coordinate Expression of Cytokines and Chemokines by NK Cells during Murine Cytomegalovirus Infection. Journal of Immunology, 172(5), 3119-3131.

Coordinate Expression of Cytokines and Chemokines by NK Cells during Murine Cytomegalovirus Infection. / Dorner, Brigitte G.; Smith, Hamish R.C.; French, Anthony R.; Kim, Sung Jin; Poursine-Laurent, Jennifer; Beckman, Diana L.; Pingel, Jeanette T.; Kroczek, Richard A.; Yokoyama, Wayne M.

In: Journal of Immunology, Vol. 172, No. 5, 01.03.2004, p. 3119-3131.

Research output: Contribution to journalArticle

Dorner, BG, Smith, HRC, French, AR, Kim, SJ, Poursine-Laurent, J, Beckman, DL, Pingel, JT, Kroczek, RA & Yokoyama, WM 2004, 'Coordinate Expression of Cytokines and Chemokines by NK Cells during Murine Cytomegalovirus Infection', Journal of Immunology, vol. 172, no. 5, pp. 3119-3131.
Dorner BG, Smith HRC, French AR, Kim SJ, Poursine-Laurent J, Beckman DL et al. Coordinate Expression of Cytokines and Chemokines by NK Cells during Murine Cytomegalovirus Infection. Journal of Immunology. 2004 Mar 1;172(5):3119-3131.
Dorner, Brigitte G. ; Smith, Hamish R.C. ; French, Anthony R. ; Kim, Sung Jin ; Poursine-Laurent, Jennifer ; Beckman, Diana L. ; Pingel, Jeanette T. ; Kroczek, Richard A. ; Yokoyama, Wayne M. / Coordinate Expression of Cytokines and Chemokines by NK Cells during Murine Cytomegalovirus Infection. In: Journal of Immunology. 2004 ; Vol. 172, No. 5. pp. 3119-3131.
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