A critical role for IL-10 in limiting inflammation during toxoplasmic encephalitis.
IL-10 plays a vital role in controlling the inflammatory response during acute Toxoplasma gondii infection, however the production of IL-10 during the chronic phase of toxoplasmosis has been associated with parasite persistence. To address this paradox, the production and effect of IL-10 in the brain during toxoplasmic encephalitis (TE) was investigated. Analysis of brain mononuclear cells (BMNC) from chronically infected mice revealed that infiltrating macrophages and CD4(+) T cells were the major sources of IL-10. Endogenous levels of IL-10 inhibited the production of IL-12, IFN-gamma, TNF-alpha, and IL-6 from both hematopoetic and non-hematopoetic cells in the brain, as well as anti-microbial activity of astrocytes. Furthermore, IL-10-/- mice that progressed to the chronic phase of infection had equivalent parasite burden to WT mice but developed a lethal inflammatory response within the brain characterized by increased numbers of CD4(+) T cells and macrophages, and elevated production of inflammatory cytokines. Finally, partial depletion of CD4(+) T cells decreased the severity of the inflammation in the brain and allowed IL-10-/- mice to survive infection. Together these results point to a vital role for IL-10 in the control of CD4(+) T cell mediated inflammation in the brain during TE.
Wilson
Emma H
EH
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104-6008, USA.
Wille-Reece
Ulrike
U
Dzierszinski
Florence
F
Hunter
Christopher A
CA
D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D015536:Down-Regulation / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D014122:Toxoplasma / Q000254:growth & development / Q000276:immunology; D016781:Toxoplasmosis, Cerebral / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*
D018836:Inflammation Mediators; D016753:Interleukin-10