Lactobacillus johnsonii alleviates colitis by TLR1/2-STAT3 mediated CD206+ macrophagesIL-10 activation

Gut Microbes. 2022 Jan-Dec;14(1):2145843. doi: 10.1080/19490976.2022.2145843.

Abstract

Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii (L. johnsonii), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10-/- mice. We identified this subset of immune cells activated by L. johnsonii as CD206+ macrophagesIL-10. Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206+ macrophagesIL-10 through the activation of STAT3 in vivo and in vitro. In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206+ macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.

Keywords: IL-10; Lactobacillus johnsonii; Macrophages; STAT3; Ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Colitis* / genetics
  • Colitis* / microbiology
  • Colitis* / therapy
  • Colitis, Ulcerative* / genetics
  • Colitis, Ulcerative* / microbiology
  • Colitis, Ulcerative* / therapy
  • Dextran Sulfate / toxicity
  • Gastrointestinal Microbiome*
  • Interleukin-10 / genetics
  • Lactobacillus johnsonii*
  • Macrophages
  • Mice
  • RNA, Ribosomal, 16S
  • Toll-Like Receptor 1* / genetics
  • Toll-Like Receptor 1* / metabolism

Substances

  • Anti-Inflammatory Agents
  • Dextran Sulfate
  • Interleukin-10
  • RNA, Ribosomal, 16S
  • Toll-Like Receptor 1
  • Tlr2 protein, mouse
  • Stat3 protein, mouse

Grants and funding

This project was financially supported by the National Foundation of Natural Science of China (82072623 to LJ Wang), Zhejiang Province Public Welfare Technology Research Project (LGD21H160002, to SJ Chen), Zhejiang Provincial Medical and Health Science and Technology Project (2019RC043 to YF Fang, 2021RC070 to L Wang) and Natural Science Foundation of Zhejiang (LQ19H030006, to HQ He).