Monocytes/macrophages and/or neutrophils are the target of IL-10 in the LPS endotoxemia model

Eur J Immunol. 2010 Feb;40(2):443-8. doi: 10.1002/eji.200939592.

Abstract

IL-10 is a potent regulator of the innate and adaptive immune responses. Several cell types produce IL-10 and its receptor chains and these may regulate different immune responses. Here we report that inactivation of the IL-10 receptor (IL-10R1) gene in mice leads to an increased susceptibility to chemically induced colitis as in the classical IL-10-deficient mutant. To identify the cells regulated by IL-10 in immune responses, we generated several cell type specific IL-10R1-deficient mutants. We show that, in an IL-10-dependent LPS model of endotoxemia, dampening of the immune response requires expression of IL-10R1 in monocytes/macrophages and/or neutrophils but not in T cells nor B cells. As the macrophage and/or neutrophil-specific IL-10-deficient mutants also display the same phenotype, our results suggest that an autocrine loop in monocytes/macrophages is the most probable mechanism for the regulation of an LPS-induced septic shock. In contrast, in an IL-10-regulated T-cell response to Trichuris muris infection, IL-10 acting on T cells or monocytes/macrophages/neutrophils is not critical for the control of the infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cecum / parasitology
  • Cecum / pathology
  • Endotoxemia / chemically induced
  • Endotoxemia / immunology
  • Endotoxemia / metabolism*
  • Female
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Lipopolysaccharides
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Receptors, Interleukin-10 / genetics
  • Receptors, Interleukin-10 / immunology
  • Receptors, Interleukin-10 / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Trichuriasis / immunology
  • Trichuriasis / parasitology
  • Trichuris / growth & development
  • Trichuris / immunology

Substances

  • Lipopolysaccharides
  • Receptors, Interleukin-10
  • Interleukin-10