Modulation of natural killer cell activity by restraint stress during an influenza A/PR8 infection in mice

John Hunzeker, David A. Padgett, Patricia A. Sheridan, Firdaus S. Dhabhar, John F. Sheridan

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

These experiments were designed to examine the influences of restraint stress (RST) on natural killer (NK) activity and to determine its consequences on influenza A/PR8 (A/PR8) viral replication in mice. The data showed that RST delayed the recruitment of NK1.1+ cells into the lung parenchyma during infection. Quantification of MIP-1α and MCP-1 gene expression by real-time PCR revealed that RST suppressed the chemokines responsible for NK cell recruitment into the infected tissue. Additionally, RST suppressed the expression of several macrophage-derived cytokines involved in the effector response of NK cells. IL-15, which is the main cytokine involved in NK cell development and homeostasis, and IL-12, which is important for NK cytotoxicity, were both suppressed. As the NK cell response is an important innate response to control viral replication, we hypothesized that the RST-mediated reduction in NK cell numbers and function would enable viral replication to continue unchecked. In fact, there was enhanced viral replication in the lungs of RST animals. Interestingly, expression of the anti-viral type I interferons (IFN-α and IFN-β) was elevated presumably in response to the elevated viral load in the stressed mice. Together, these data show that RST suppressed expression of the cytokine genes involved in the recruitment and activation of NK cells during an experimental influenza viral infections. The consequence of this effect was diminished NK cell function and enhanced viral replication.

Original languageEnglish (US)
Pages (from-to)526-535
Number of pages10
JournalBrain, Behavior, and Immunity
Volume18
Issue number6
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

Keywords

  • Chemokines
  • IL-12
  • IL-15
  • Natural killer cells
  • Stress
  • Type I interferons

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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