Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Mol Nutr Food Res. 2014 Oct;58(10):2080-93. doi: 10.1002/mnfr.201400218. Epub 2014 Aug 5.
Immunobiotics are known to modulate intestinal immune responses by regulating Toll-like 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.
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 ETEC mediated mitogen-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.
Ld and its EPS have the potential to be used for the development of anti-inflammatory functional foods to prevent intestinal diseases in both humans and animals.
免疫生物制剂通过调节 Toll 样受体（TLR）信号通路来调节肠道免疫反应，该通路负责诱导细胞因子和趋化因子对微生物相关分子模式的反应。然而，对于免疫生物制剂中的化合物或分子的免疫调节活性知之甚少。
我们评估了德氏乳杆菌亚种。delbrueckii TUA4408L（Ld）或其细胞外多糖（EPS）：酸性 EPS（APS）和中性 EPS（NPS）是否调节猪肠上皮细胞（PIE）细胞对肠产毒性大肠杆菌（ETEC）987P 的反应。还研究了 TLR2、TLR4 和 TLR 负调节因子在免疫调节作用中的作用。当 PIE 细胞用 Ld 或 EPS 预先刺激时，ETEC 诱导的炎症细胞因子下调。Ld、APS 和 NPS 通过上调 TLR 负调节因子抑制 ETEC 介导的丝裂原活化蛋白激酶（MAPK）和核因子-κB（NF-κB）激活。当 PIE 细胞用抗 TLR2 抗体阻断时，Ld 抑制炎症细胞因子的能力减弱，而当细胞用抗 TLR4 抗体处理时，APS 未能抑制炎症细胞因子。TLR 敲低细胞中 Ca²⁺通量的诱导证实 TLR2 在 Ld 的免疫调节作用中起主要作用，而 APS 的活性由 TLR4 介导。此外，NPS 的活性取决于 TLR4 和 TLR2。
Ld 及其 EPS 有可能被用于开发抗炎功能性食品，以预防人类和动物的肠道疾病。
