Systemic but not local infections elicit immunosuppressive IL-10 production by natural killer cells.
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.
Perona-Wright
Georgia
G
Trudeau Institute, Saranac Lake, NY 12983, USA.
Mohrs
Katja
K
Szaba
Frank M
FM
Kummer
Lawrence W
LW
Madan
Rajat
R
Karp
Christopher L
CL
Johnson
Lawrence L
LL
Smiley
Stephen T
ST
Mohrs
Markus
M
D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D007166:Immunosuppressive Agents / Q000276:immunology*; D007239:Infections / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014122:Toxoplasma / Q000276:immunology; D015010:Yersinia pestis / Q000276:immunology
D007166:Immunosuppressive Agents; D016753:Interleukin-10; D018664:Interleukin-12