Tyndallized bacteria prime bronchial epithelial cells to mount an effective innate immune response against infections

Hum Cell. 2024 Jul;37(4):1080-1090. doi: 10.1007/s13577-024-01080-z. Epub 2024 May 30.

Abstract

Airway epithelium represents a physical barrier against toxic substances and pathogens but also presents pattern recognition receptors on the epithelial cells that detect pathogens leading to molecule release and sending signals that activate both the innate and adaptive immune responses. Thus, impaired airway epithelial function and poor integrity may increase the recurrence of infections. Probiotic use in respiratory diseases as adjuvant of traditional therapy is increasingly widespread. There is growing interest in the use of non-viable heat-killed bacteria, such as tyndallized bacteria (TB), due to safety concerns and to their immunomodulatory properties. This study explores in vitro the effects of a TB blend on the immune activation of airway epithelium. 16HBE bronchial epithelial cells were exposed to different concentrations of TB. Cell viability, TB internalization, TLR2 expression, IL-6, IL-8 and TGF-βl expression/release, E-cadherin expression and wound healing were assessed. We found that TB were tolerated, internalized, increased TLR2, E-cadherin expression, IL-6 release and wound healing but decreased both IL-8 and TGF-βl release. In conclusion, TB activate TLR2 pathway without inducing a relevant pro-inflammatory response and improve barrier function, leading to the concept that TB preserve epithelial homeostasis and could be used as strategy to prevent and to manage respiratory infection, exacerbations included.

Keywords: Bronchial epithelial cells; Epithelial homeostasis; Innate immune responses; Tyndallized bacteria.

MeSH terms

  • Bronchi* / cytology
  • Bronchi* / immunology
  • Cadherins / metabolism
  • Cell Survival
  • Cells, Cultured
  • Epithelial Cells* / immunology
  • Epithelial Cells* / metabolism
  • Gene Expression
  • Humans
  • Immunity, Innate*
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Probiotics
  • Respiratory Mucosa / immunology
  • Respiratory Tract Infections / immunology
  • Respiratory Tract Infections / microbiology
  • Toll-Like Receptor 2* / metabolism

Substances

  • Toll-Like Receptor 2
  • TLR2 protein, human
  • Interleukin-6
  • Cadherins
  • Interleukin-8