Genetically engineered Lactococcus lactis secreting murine IL-10 modulates the functions of bone marrow-derived dendritic cells in the presence of LPS.
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.
Loos
M
M
Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
Remaut
E
E
Rottiers
P
P
De Creus
A
A
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005818:Genetic Engineering; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D013294:Lactococcus lactis / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000494:pharmacology*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020381:Interleukin-17; D053759:Interleukin-23; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12