Fecal bacteria from treatment-naive Crohn's disease patients can skew helper T cell responses

Exp Cell Res. 2017 Dec 1;361(1):135-140. doi: 10.1016/j.yexcr.2017.10.011. Epub 2017 Oct 12.

Abstract

Many studies have demonstrated that the inflamed mucosa of Crohn's disease (CD) patients presented a disturbed gut commensal community, and the shift in microbial composition and species variety is associated with disease severity. To establish a link between changes in the intestinal bacterial composition and the alteration of inflammation, we obtained fecal bacteria from CD patients and non-CD controls. The bacteria were then used to stimulate the peripheral blood mononuclear cells (PBMCs) from one non-CD individual. We found that the frequency of IFN-γ- and IL-17-expressing CD4 T cells was significantly higher after stimulation with CD bacteria than with non-CD bacteria, while the frequency of IL-4- and IL-10-expressing CD4 T cells was significantly decreased after stimulation with CD bacteria. A similar trend was observed in the level of cytokine expression and transcription expression. However, this difference was not clear-cut, as overlapping regions were observed between the two groups. With longer stimulation using CD bacteria, the skewing toward Th1/Th17 responses were further increased. This increase depended on the presence of monocytes/macrophages. Interestingly, we also found that B cells presented an inhibitory effect in CD bacteria-mediated skewing toward Th1/Th17 cells and promoted IL-10 secretion in CD bacteria-stimulated PBMCs. Together, our results demonstrated that CD bacteria could promote Th1/Th17 inflammation in a host factor-independent fashion.

Keywords: Bacteria; Crohn's disease; Helper T cell.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B-Lymphocytes / immunology
  • B-Lymphocytes / microbiology
  • Bacteria*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / microbiology
  • Case-Control Studies
  • Cells, Cultured
  • Crohn Disease / immunology*
  • Crohn Disease / microbiology
  • Cytokines / metabolism
  • Feces / microbiology*
  • Female
  • Humans
  • Leukocytes, Mononuclear
  • Male
  • Middle Aged
  • Th1 Cells / immunology*
  • Th1 Cells / microbiology
  • Th17 Cells / immunology*
  • Th17 Cells / microbiology
  • Young Adult

Substances

  • Cytokines