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通过转录组分析破译副免疫双歧杆菌对牛肠上皮细胞固有抗病毒免疫反应的影响。

Deciphering the influence of paraimmunobiotic bifidobacteria on the innate antiviral immune response of bovine intestinal epitheliocytes by transcriptomic analysis.

机构信息

1 Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Chacabuco 145, Tucuman 4000, Argentina.

2 Immunobiotics Research Group, Graduate School of Agricultural Science, Tohoku University, Sendai 984-0051, Japan.

出版信息

Benef Microbes. 2019 Mar 13;10(2):199-209. doi: 10.3920/BM2018.0024. Epub 2018 Dec 10.

DOI:10.3920/BM2018.0024
PMID:30860402
Abstract

Previously, we reported that the non-viable immunomodulatory Bifidobacterium infantis MCC12 and Bifidobacterium breve MCC1274 strains (paraimmunobiotic bifidobacteria) were able to increase the protection against rotavirus infection in bovine intestinal epithelial (BIE) cells. In order to gain insight into the influence of paraimmunobiotic bifidobacteria on the innate antiviral immune response of BIE cells, their effect on the transcriptomic response triggered by Toll-like receptor 3 (TLR3) activation was investigated. By using microarray technology and qPCR analysis, we obtained a global overview of the immune genes involved in the innate antiviral immune response in BIE cells. Activation of TLR3 by poly(I:C) in BIE cells significantly increased the expression of interferon (IFN)-α and IFN-β, several interferon-stimulated genes, cytokines, and chemokines. It was also observed that both paraimmunobiotic bifidobacteria differently modulated immune genes expression in poly(I:C)-challenged BIE cells. Most notable changes were found in genes involved in antiviral defence (IFN-β, MX1, OAS1X, MDA5, TLR3, STAT2, STAT3), cytokines (interleukin (IL)-6), and chemokines (CCL2, CXCL2, CXCL6) that were significantly increased in bifidobacteria-treated BIE cells. B. infantis MCC12 and B. breve MCC1274 showed quantitative and qualitative differences in their capacities to modulate the innate antiviral immune response in BIE cells. B. breve MCC1274 was more efficient than the MCC12 strain to improve the production of type I IFNs and antiviral factors, an effect that could be related to its higher ability to protect against rotavirus replication in BIE cells. Interestingly, B. infantis MCC12 showed a remarkable anti-inflammatory effect. The MCC12 strain was more efficient to reduce the expression of inflammatory cytokines and chemokines (IL-16, IL-20, CX3CL1) when compared with B. breve MCC1274. These results provided valuable information for the deeper understanding of the antiviral immune response of intestinal epithelial cells as well as the host-paraimmunobiotic interaction in the bovine host.

摘要

先前,我们曾报道过非存活的免疫调节双歧杆菌婴儿型 MCC12 和短双歧杆菌 MCC1274 菌株(副免疫双歧杆菌)能够增加牛肠上皮细胞(BIE)对轮状病毒感染的保护。为了深入了解副免疫双歧杆菌对 BIE 细胞固有抗病毒免疫反应的影响,我们研究了它们对 Toll 样受体 3(TLR3)激活引发的转录组反应的影响。通过使用微阵列技术和 qPCR 分析,我们获得了 BIE 细胞固有抗病毒免疫反应中涉及的免疫基因的全景图。TLR3 激活 Poly(I:C)在 BIE 细胞中显著增加了干扰素(IFN)-α和 IFN-β、几种干扰素刺激基因、细胞因子和趋化因子的表达。还观察到,两种副免疫双歧杆菌在 Poly(I:C)挑战的 BIE 细胞中不同地调节免疫基因的表达。在 IFN-β、MX1、OAS1X、MDA5、TLR3、STAT2、STAT3 等抗病毒防御相关基因、细胞因子(白细胞介素(IL)-6)和趋化因子(CCL2、CXCL2、CXCL6)的表达方面发现了最显著的变化,这些基因在双歧杆菌处理的 BIE 细胞中显著增加。B. infantis MCC12 和 B. breve MCC1274 在调节 BIE 细胞固有抗病毒免疫反应的能力方面表现出定量和定性的差异。B. breve MCC1274 比 MCC12 菌株更有效地提高 I 型 IFNs 和抗病毒因子的产生,这种效应可能与其在 BIE 细胞中更有效地抑制轮状病毒复制有关。有趣的是,B. infantis MCC12 表现出显著的抗炎作用。与 B. breve MCC1274 相比,MCC12 菌株更有效地降低了炎症细胞因子和趋化因子(IL-16、IL-20、CX3CL1)的表达。这些结果为深入了解肠道上皮细胞的抗病毒免疫反应以及牛宿主中的宿主-副免疫相互作用提供了有价值的信息。

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