Bifidobacterium infantis Induces Protective Colonic PD-L1 and Foxp3 Regulatory T Cells in an Acute Murine Experimental Model of Inflammatory Bowel Disease

Gut Liver. 2019 Mar 15;13(4):430-439. doi: 10.5009/gnl18316.

Abstract

Background/aims: The current study aims to investigate the protective effects of Bifidobacterium infantis on the abnormal immune response to inflammatory bowel disease (IBD) in dextran sodium sulfate (DSS)-induced colitis.

Methods: Eight-week-old BALB/c mice were separated into five groups at random (control, DSS, DSS+B9 [B. infantis 1×109 CFU], DSS+B8 [B. infantis 1×108 CFU], and DSS+B7 [B. infantis 1×107 CFU]). Colitis was induced by 5% DSS ad libitum for 7 days, at which time we assessed weight, the disease activity index (DAI) score, and the histological damage score. The nuclear transcription factor Foxp3 (a marker of Treg cells), cytokines interleukin-10 (IL-10) and transforming growth factor β1 (TGF-β1), and related proteins (programmed cell death ligand 1 [PD-L1] and programmed cell death 1 [PD-1]) were detected by an immunohistochemical method and Western blot.

Results: B. infantis increased weight, decreased DAI scores and histological damage scores, increased the protein expression of Foxp3 (p<0.05) and cytokines IL-10 and TGF-β1 in mouse colon tissue (p<0.05), and increased the expression of PD-L1 in the treatment groups relative to that in the DSS group (p<0.05). The effect of B. infantis on Foxp3 and PD-L1 was dose dependent in the treatment groups (p<0.05). PD-L1 was positively correlated with Foxp3, IL-10, and TGF-β1.

Conclusions: In a mouse model of IBD, B. infantis can alleviate intestinal epithelial injury and maintain intestinal immune tolerance and thus may have potential therapeutic value for the treatment of immune damage in IBD.

Keywords: Bifidobacterium infantis; Inflammatory bowel disease; Programmed cell death ligand 1; T-Lymphocytes; regulatory.

MeSH terms

  • Animals
  • B7-H1 Antigen / immunology
  • Bifidobacterium longum subspecies infantis*
  • Colitis / immunology*
  • Colitis / microbiology
  • Colitis / pathology
  • Dextran Sulfate
  • Forkhead Transcription Factors / immunology
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / microbiology
  • Inflammatory Bowel Diseases / pathology
  • Interleukin-10 / immunology
  • Mice
  • Probiotics*
  • Programmed Cell Death 1 Receptor / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta1 / immunology

Substances

  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • IL10 protein, mouse
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • Interleukin-10
  • Dextran Sulfate