Coordinated control of immunity to muscle stage Trichinella spiralis by IL-10, regulatory T cells, and TGF-beta

J Immunol. 2007 Jan 15;178(2):1039-47. doi: 10.4049/jimmunol.178.2.1039.

Abstract

We previously demonstrated that IL-10 is critical in the control of acute inflammation during development of Trichinella spiralis in the muscle. In this study, we use gene-targeted knockout mice, adoptive transfer of specific T cell populations, and in vivo Ab treatments to determine the mechanisms by which inflammation is controlled and effector T cell responses are moderated during muscle infection. We report that CD4(+)CD25(-) effector T cells, rather than CD4(+)CD25(+) regulatory T cells, suppress inflammation by an IL-10-dependent mechanism that limits IFN-gamma production and local inducible NO synthase induction. Conversely, we show that depletion of regulatory T cells during infection results in exaggerated Th2 responses. Finally, we provide evidence that, in the absence of IL-10, TGF-beta participates in control of local inflammation in infected muscle and promotes parasite survival.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Polarity
  • Cell Survival
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myositis / immunology*
  • Myositis / metabolism
  • Myositis / parasitology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th2 Cells / cytology
  • Th2 Cells / immunology
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism*
  • Trichinella spiralis / immunology*
  • Trichinellosis / genetics
  • Trichinellosis / immunology*
  • Trichinellosis / metabolism*
  • Trichinellosis / pathology

Substances

  • Transforming Growth Factor beta
  • Interleukin-10
  • Interferon-gamma