Systemic but not local infections elicit immunosuppressive IL-10 production by natural killer cells

Cell Host Microbe. 2009 Dec 17;6(6):503-12. doi: 10.1016/j.chom.2009.11.003.


Surviving infection represents a balance between the proinflammatory responses needed to eliminate the pathogen, and anti-inflammatory signals limiting damage to the host. IL-10 is a potent immunosuppressive cytokine whose impact is determined by the timing and localization of release. We show that NK cells rapidly express IL-10 during acute infection with diverse rapidly disseminating pathogens. The proinflammatory cytokine IL-12 was necessary and sufficient for NK cell induction of IL-10. NK cells from mice with systemic parasitic infection inhibited dendritic cell release of IL-12 in an IL-10-dependent manner, and NK cell depletion resulted in elevated serum IL-12. These data suggest an innate, negative feedback loop in which IL-12 limits its own production by eliciting IL-10 from NK cells. In contrast to disseminating pathogens, locally restricted infections did not elicit NK cell IL-10. Thus systemic infections uniquely engage NK cells in an IL-10-mediated immunoregulatory circuit that functions to alleviate inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Gene Expression
  • Immunosuppressive Agents / immunology*
  • Infections / immunology*
  • Infections / microbiology
  • Infections / parasitology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Killer Cells, Natural / immunology*
  • Listeria monocytogenes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Toxoplasma / immunology
  • Yersinia pestis / immunology


  • Immunosuppressive Agents
  • Interleukin-10
  • Interleukin-12