Enteroglial-derived S100B protein integrates bacteria-induced Toll-like receptor signalling in human enteric glial cells

Gut. 2014 Jan;63(1):105-15. doi: 10.1136/gutjnl-2012-302090. Epub 2013 Jan 3.


Objective: Enteric glial cells (EGC) have been suggested to participate in host-bacteria cross-talk, playing a protective role within the gut. The way EGC interact with microorganisms is still poorly understood. We aimed to evaluate whether: EGC participate in host-bacteria interaction; S100B and Toll-like receptor (TLR) signalling converge in a common pathway leading to nitric oxide (NO) production.

Design: Primary cultures of human EGC were exposed to pathogenic (enteroinvasive Escherichia coli; EIEC) and probiotic (Lactobacillus paracasei F19) bacteria. Cell activation was assessed by evaluating the expression of cFos and major histocompatibility complex (MHC) class II molecules. TLR expression in EGC was evaluated at both baseline and after exposure to bacteria by real-time PCR, fluorescence microscopy and western blot analysis. S100B expression and NO release from EGC, following exposure to bacteria, were measured in the presence or absence of specific TLR and S100B pathway inhibitors.

Results: EIEC activated EGC by inducing the expression of cFos and MHC II. EGC expressed TLR at baseline. Pathogens and probiotics differentially modulated TLR expression in EGC. Pathogens, but not probiotics, significantly induced S100B protein overexpression and NO release from EGC. Pretreatment with specific inhibitors of TLR and S100B pathways abolished bacterial-induced NO release from EGC.

Conclusions: Human EGC interact with bacteria and discriminate between pathogens and probiotics via a different TLR expression and NO production. In EGC, NO release is impaired in the presence of specific inhibitors of the TLR and S100B pathways, suggesting the presence of a novel common pathway involving both TLR stimulation and S100B protein upregulation.

Keywords: Enteric Bacterial Microflora; Enteric Nervous System; Nervous Control of Intestinal Functions; Nitric Oxide; Probiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • Blotting, Western
  • Cells, Cultured
  • Escherichia coli / metabolism*
  • Female
  • Host-Pathogen Interactions*
  • Humans
  • Intestine, Small / metabolism
  • Intestine, Small / microbiology*
  • Lactobacillus / metabolism*
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Neuroglia / metabolism
  • Neuroglia / microbiology*
  • Nitric Oxide / metabolism
  • Probiotics / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Calcium Binding Protein beta Subunit / metabolism*
  • Signal Transduction
  • Toll-Like Receptors / metabolism*


  • Biomarkers
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • Toll-Like Receptors
  • Nitric Oxide