Genetically engineered Lactococcus lactis secreting murine IL-10 modulates the functions of bone marrow-derived dendritic cells in the presence of LPS

Scand J Immunol. 2009 Feb;69(2):130-9. doi: 10.1111/j.1365-3083.2008.02206.x. Epub 2008 Dec 22.

Abstract

Oral delivery of IL-10 by genetically modified Lactococcus lactis (LL-pTmIL10) has been shown to efficiently reduce intestinal inflammation in mice with chronic colitis, but the mechanisms involved have not been elucidated. It has been suggested that IL-10 controls intestinal inflammation by inhibiting microbe-induced activation of dendritic cells. We therefore investigated whether LL-pTmIL10 can modulate the functions of bone marrow-derived dendritic cells (BM-DC) responding to LPS. Incubation of these cells with LL-pTmIL10 or with the control strain LL-pTREX reduced their ability to activate allogeneic T-cell proliferation. However, in contrast to LL-pTREX, LL-pTmIL10 inhibited the LPS-stimulated secretion of MCP-1 by BM-DC and reduced the synergistic up-regulation of IL-12/IL-23p40. In addition, LL-pTmIL10 treatment of LPS-stimulated BM-DC significantly inhibited their capacity to induce strong secretion of IL-17 by CD4+ T cells. Our data suggest that the beneficial effects of LL-pTmIL10 treatment during chronic colitis might involve inhibition of CD4+ Th17 cells and a reduced accumulation of these cells as well as other immune cells at the site of inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / physiology
  • Chemokine CCL2 / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / physiology
  • Female
  • Genetic Engineering
  • Interleukin-10 / physiology*
  • Interleukin-12 / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-23 / metabolism
  • Lactococcus lactis / genetics*
  • Lipopolysaccharides / pharmacology*
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Probiotics / pharmacology*

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Interleukin-17
  • Interleukin-23
  • Lipopolysaccharides
  • Interleukin-10
  • Interleukin-12