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

Perona-Wright, G. , Mohrs, K., Szaba, F. M., Kummer, L. W., Madan, R., Karp, C. L., Johnson, L. L., Smiley, S. T. and Mohrs, M. (2009) Systemic but not local infections elicit immunosuppressive IL-10 production by natural killer cells. Cell Host and Microbe, 6(6), pp. 503-512. (doi: 10.1016/j.chom.2009.11.003) (PMID:20006839) (PMCID:PMC2796259)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Perona-Wright, Dr Georgia
• Authors: Perona-Wright, G., Mohrs, K., Szaba, F. M., Kummer, L. W., Madan, R., Karp, C. L., Johnson, L. L., Smiley, S. T., and Mohrs, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Cell Host and Microbe
• Publisher: Elsevier
• ISSN: 1931-3128
• ISSN (Online): 1934-6069
• Published Online: 16 December 2009