Distinctive probiotic features share common TLR2-dependent signalling in intestinal epithelial cells

Cell Microbiol. 2021 Jan;23(1):e13264. doi: 10.1111/cmi.13264. Epub 2020 Oct 1.

Abstract

The underlying mechanisms of probiotics and postbiotics are not well understood, but it is known that both affect the adaptive and innate immune responses. In addition, there is a growing concept that some probiotic strains have common core mechanisms that provide certain health benefits. Here, we aimed to elucidate the signalization of the probiotic bacterial strains Lactobacillus paragasseri K7, Limosilactobacillus fermentum L930BB, Bifidobacterium animalis subsp. animalis IM386 and Lactiplantibacillus plantarum WCFS1. We showed in in vitro experiments that the tested probiotics exhibit common TLR2- and TLR10-dependent downstream signalling cascades involving inhibition of NF-κB signal transduction. Under inflammatory conditions, the probiotics activated phosphatidylinositol 3-kinase (PI3K)/Akt anti-apoptotic pathways and protein kinase C (PKC)-dependent pathways, which led to regulation of the actin cytoskeleton and tight junctions. These pathways contribute to the regeneration of the intestinal epithelium and modulation of the mucosal immune system, which, together with the inhibition of canonical TLR signalling, promote general immune tolerance. With this study we identified shared probiotic mechanisms and were the first to pinpoint the role of anti-inflammatory probiotic signalling through TLR10.

Keywords: Bifidobacterium; Lactobacillus; TLR10; innate immunity; postbiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / microbiology
  • HEK293 Cells
  • HT29 Cells
  • Host Microbial Interactions
  • Humans
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Probiotics / pharmacology*
  • Protein Kinase C / metabolism
  • Signal Transduction*
  • Toll-Like Receptor 10 / metabolism*
  • Toll-Like Receptor 2 / metabolism*

Substances

  • NF-kappa B
  • TLR10 protein, human
  • TLR2 protein, human
  • Toll-Like Receptor 10
  • Toll-Like Receptor 2
  • Protein Kinase C