Lactobacillus delbrueckii TUA4408L and its extracellular polysaccharides attenuate enterotoxigenic Escherichia coli-induced inflammatory response in porcine intestinal epitheliocytes via Toll-like receptor-2 and 4

Satoshi Wachi, Paulraj Kanmani, Yohsuke Tomosada, Hisakazu Kobayashi, Toshihito Yuri, Shintaro Egusa, Tomoyuki Shimazu, Yoshihito Suda, Hisashi Aso, Makoto Sugawara, Tadao Saito, Takashi Mishima, Julio Villena, Haruki Kitazawa

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Scope: Immunobiotics are known tomodulate intestinal immune responses by regulating Tolllike receptor (TLR) signaling pathways, which are responsible for the induction of cytokines and chemokines in response to microbial-associated molecular patterns. However, little is known about the immunomodulatory activity of compounds or molecules from immunobiotics. Methods and results: We evaluated whether Lactobacillus delbrueckii subsp. delbrueckii TUA4408L (Ld) or its extracellular polysaccharide (EPS): acidic EPS (APS) and neutral EPS (NPS), modulated the response of porcine intestinal epitheliocyte (PIE) cells against Enterotoxigenic Escherichia coli (ETEC) 987P. The roles of TLR2, TLR4, and TLR negative regulators in the immunoregulatory effects were also studied. ETEC-induced inflammatory cytokines were downregulated when PIE cells were prestimulated with both Ld or EPSs. Ld, APS, and NPS inhibited ETECmediatedmitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) activation by upregulating TLR negative regulators. The capability of Ld to suppress inflammatory cytokines was diminished when PIE cells were blocked with anti-TLR2 antibody, while APS failed to suppress inflammatory cytokines when cells were treated with anti-TLR4 antibody. Induction of Ca2+ fluxes in TLR knockdown cells confirmed that TLR2 plays a principal role in the immunomodulatory action of Ld, while the activity of APS is mediated by TLR4. In addition, NPS activity depends on both TLR4 and TLR2. Conclusion: Ld and its EPS have the potential to be used for the development of antiinflammatory functional foods to prevent intestinal diseases in both humans and animals.

Original languageEnglish
Pages (from-to)2080-2093
Number of pages14
JournalMolecular Nutrition and Food Research
Volume58
Issue number10
DOIs
Publication statusPublished - 2014 Oct

Keywords

  • Anti-inflammatory activity
  • Extracellular polysaccharides
  • L. delbrueckii
  • PIE cells
  • TLR negative regulators
  • TLR2
  • TLR4

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

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