Immunobiotic Lactobacillus jensenii Modulates the Toll-Like Receptor 4-Induced Inflammatory Response via Negative Regulation in Porcine Antigen-Presenting Cells
Immunobiotic Lactobacillus jensenii Modulates the Toll-Like Receptor 4-Induced Inflammatory Response via Negative Regulation in Porcine Antigen-Presenting Cells
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DOI：
10.1128/cvi.00199-12
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发表时间：
2012-07-01
影响因子：
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通讯作者：
Kitazawa, Haruki
中科院分区：
文献类型：
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作者：
Villena, Julio;Suzuki, Rie;Kitazawa, Haruki
以前，我们证明了詹氏乳杆菌TL 2937减弱猪肠上皮细胞中Toll样受体4（TLR-4）激活引发的炎症反应。鉴于抗原提呈细胞（APC）极化在免疫调节中的重要性，本研究的目的是检测TL 2937菌株对猪派伊尔集合淋巴结（PP）APC激活模式的影响。我们证明了猪APC直接暴露于L。在没有炎症信号的情况下，jensenii增加了CD 172 a（+）APC中白细胞介素-10（IL-10）和转化生长因子β的表达，并使它们显示出致耐受性特性。此外，用L. jensenii导致响应于TLR 4活化的促炎细胞因子和抗炎细胞因子的产生的差异调节。菌株TL 2937的免疫调节作用与TLR 4的下调无关，但与TLR的三种负调节因子的表达上调有关：单免疫球蛋白IL-1相关受体（SIGIRR）、A20和白细胞介素-1受体相关激酶M（IRAK-M）。我们的研究结果还表明，TLR 2在L. jensenii TL 2937，因为抗TLR 2抗体阻断了CD 172 a（+）APC中SIGIRR和IRAK-M的上调以及响应于TLR 4活化的IL-10的产生。我们首次对来自PP的猪APC进行了精确的功能表征，并证明了CD 172 a（+）细胞是耐受原性的。我们的研究结果表明，贴壁细胞和分离的CD 172 a（+）细胞收集猪PP是有用的，在猪肠道的炎症反应和免疫生物微生物的免疫调节作用的体外研究。
Previously, we demonstrated that Lactobacillus jensenii TL2937 attenuates the inflammatory response triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal epithelial cells. In view of the critical importance of antigen-presenting cell (APC) polarization in immunoregulation, the objective of the present study was to examine the effect of strain TL2937 on the activation patterns of APCs from swine Peyer's patches (PPs). We demonstrated that direct exposure of porcine APCs to L. jensenii in the absence of inflammatory signals increased expression of interleukin-10 (IL-10) and transforming growth factor beta in CD172a(+) APCs and caused them to display tolerogenic properties. In addition, pretreatment of CD172a(+) APCs with L. jensenii resulted in differential modulation of the production of pro-and anti-inflammatory cytokines in response to TLR4 activation. The immunomodulatory effect of strain TL2937 was not related to a downregulation of TLR4 but was related to an upregulation of the expression of three negative regulators of TLRs: single immunoglobulin IL-1-related receptor (SIGIRR), A20, and interleukin-1 receptor-associated kinase M(IRAK-M). Our results also indicated that TLR2 has an important role in the anti-inflammatory activity of L. jensenii TL2937, since anti-TLR2 antibodies blocked the upregulation of SIGIRR and IRAK-M in CD172a(+) APCs and the production of IL-10 in response to TLR4 activation. We performed, for the first time, a precise functional characterization of porcine APCs from PPs, and we demonstrated that CD172a(+) cells were tolerogenic. Our findings demonstrate that adherent cells and isolated CD172a(+) cells harvested from swine PPs were useful for in vitro study of the inflammatory responses in the porcine gut and the immunomodulatory effects of immunobiotic microorganisms.