Kanmani Paulraj, Albarracin Leonardo, Kobayashi Hisakazu, Iida Hikaru, Komatsu Ryoya, Humayun Kober A K M, Ikeda-Ohtsubo Wakako, Suda Yoshihito, Aso Hisashi, Makino Seiya, Kano Hiroshi, Saito Tadao, Villena Julio, Kitazawa Haruki
Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina.
Mol Immunol. 2018 Jan;93:253-265. doi: 10.1016/j.molimm.2017.07.009. Epub 2017 Aug 8.
Previous studies demonstrated that the extracellular polysaccharides (EPSs) produced by Lactobacillus delbrueckii OLL1073R-1 (LDR-1) improve antiviral immunity, especially in the systemic and respiratory compartments. However, it was not studied before whether those EPSs are able to beneficially modulate intestinal antiviral immunity. In addition, LDR-1-host interaction has been evaluated mainly with immune cells while its interaction with intestinal epithelial cells (IECs) was not addressed before. In this work, we investigated the capacity of EPSs from LDR-1 to modulate the response of porcine IECs (PIE cells) to the stimulation with the Toll-like receptor (TLR)-3 agonist poly(I:C) and the role of TLR2, TLR4, and TLR negative regulators in the immunoregulatory effect. We showed that innate immune response triggered by TLR3 activation in porcine IECs was differentially modulated by EPS from LDR-1. EPSs treatment induced an increment in the expression of interferon (IFN)-α and IFN-β in PIE cells after the stimulation with poly(I:C) as well as the expression of the antiviral factors MxA and RNase L. Those effects were related to the reduced expression of A20 in EPS-treated PIE cells. EPS from LDR-1 was also able to reduce the expression of IL-6 and proinflammatory chemokines. Although further in vivo studies are needed, our results suggest that these EPSs or a yogurt fermented with LDR-1 have potential to improve intestinal innate antiviral response and protect against intestinal viruses.
先前的研究表明，德氏乳杆菌OLL1073R-1（LDR-1）产生的胞外多糖（EPSs）可改善抗病毒免疫力，尤其是在全身和呼吸道部位。然而，此前尚未研究这些EPSs是否能够有益地调节肠道抗病毒免疫力。此外，LDR-1与宿主的相互作用主要是通过免疫细胞进行评估的，而其与肠道上皮细胞（IECs）的相互作用此前并未涉及。在这项研究中，我们研究了LDR-1产生的EPSs调节猪IECs（PIE细胞）对Toll样受体（TLR）-3激动剂聚肌胞苷酸（poly(I:C)）刺激的反应的能力，以及TLR2、TLR4和TLR负调节因子在免疫调节作用中的作用。我们发现，LDR-1产生的EPSs对猪IECs中由TLR3激活引发的先天性免疫反应具有不同的调节作用。在用poly(I:C)刺激后，EPSs处理可诱导PIE细胞中干扰素（IFN）-α和IFN-β的表达增加，以及抗病毒因子Mx A和核糖核酸酶L的表达增加。这些作用与EPS处理的PIE细胞中A20表达的降低有关。LDR-1产生的EPSs还能够降低IL-6和促炎趋化因子的表达。尽管还需要进一步的体内研究，但我们的结果表明，这些EPSs或用LDR-1发酵的酸奶有潜力改善肠道先天性抗病毒反应并预防肠道病毒感染。
