Inhibition of NKG2D expression in NK cells by cytokines secreted in response to human cytomegalovirus infection

Aura Muntasell, Giuliana Magri, Daniela Pende, Ana Angulo, Miguel López-Botet

Research output: Contribution to journalArticlepeer-review

Abstract

The NKG2D receptor activates natural killer (NK) cell cytotoxicity and cytokine production on recognition of self-molecules induced by cellular stress under different conditions such as viral infections. The importance of NKG2D in the immune response to human cytomegalovirus (HCMV) is supported by the identification of several viral molecules that prevent the expression of NKG2D ligands by infected cells. In this study we report that, paradoxically, a significant, selective, and transient reduction of NKG2D expression on NK cells is detected during HCMV infection of peripheral blood mononuclear cells if needed. Antagonizing type I interferon (IFN), interleukin-12 (IL-12), and IFNγ prevented HCMV-induced down-regulation of surface NKG2D. Moreover, treatment of purified NK cells with recombinant IFNβ1 and IL-12 mimicked the effect, supporting a direct role of these cytokines in regulating NKG2D surface expression in NK cells. The loss of NKG2D expression selectively impaired NK-cell cytotoxicity against cells expressing NKG2D ligands but preserved the response triggered through other activating receptors. These results support that down-regulation of NKG2D expression on NK cells by cytokines with a key role in antiviral immune response may constitute a physiologic mechanism to control NK-cell reactivity against normal cells expressing NKG2D ligands in the context of inflammatory responses to viral infections.

Original languageEnglish
Pages (from-to)5170-5179
Number of pages10
JournalBlood
Volume115
Issue number25
DOIs
Publication statusPublished - Jun 24 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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