Bacterial Teichoic Acids Reverse Predominant IL-12 Production Induced by Certain Lactobacillus Strains into Predominant IL-10 Production via TLR2-Dependent ERK Activation in Macrophages
Bacterial Teichoic Acids Reverse Predominant IL-12 Production Induced by Certain Lactobacillus Strains into Predominant IL-10 Production via TLR2-Dependent ERK Activation in Macrophages
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DOI：
10.4049/jimmunol.0901569
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发表时间：
2010-04-01
影响因子：
4.4
通讯作者：
Shida, Kan
中科院分区：
文献类型：
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作者：
Kaji, Rumi;Kiyoshima-Shibata, Junko;Shida, Kan
巨噬细胞对益生菌乳酸杆菌的细胞因子应答因菌株而异，并且IL-10/IL-12产生的平衡对于确定免疫应答的方向至关重要。为了阐明乳杆菌菌株差异诱导IL-10和IL-12产生的机制，我们研究了细胞因子产生和MAPK活化之间的潜在关系。在小鼠腹腔巨噬细胞中，植物乳杆菌可有效诱导IL-10的产生，但诱导IL-12的产生较弱，而L.干酪素有效地诱导IL-12的产生，但弱地诱导IL-10的产生。对ERK、p38和JNK激活的动力学分析表明，L. plantarum比L. casei。选择性阻断植物乳杆菌诱导的ERK激活导致IL-10产生减少，同时IL-12产生增加。有趣的是，当巨噬细胞被L。植物L. casei，协同诱导IL-10的产生。我们确定细胞壁磷壁酸和脂磷壁酸作为触发IL-10产生的协同诱导的关键因素，尽管这些磷壁酸单独仅弱诱导IL-10产生。这些磷壁酸对IL-10产生的作用是通过TLR 2依赖性ERK激活介导的。我们的数据表明，ERK通路的激活对于确定巨噬细胞对乳酸杆菌的IL-10 AL-12应答的平衡是至关重要的，并且某些乳酸杆菌如L.当在磷壁酸存在下刺激时，酪蛋白可转化为主要的IL-10产生。免疫学杂志，2010，184：3505-3513。
The cytokine response of macrophages to probiotic lactobacilli varies between strains, and the balance of IL-10/IL-12 production is crucial for determination of the direction of the immune response. To clarify the mechanism whereby Lactobacillus strains differentially induce production of IL-10 and IL-12, we examined the potential relationship between cytokine production and MAPK activation. In mouse peritoneal macrophages, Lactobacillus plantarum potently induced IL-10 but weakly induced IL-12 production, whereas L. casei potently induced IL-12 but weakly induced IL-10 production. Kinetic analysis of the activation of ERK, p38, and JNK showed that L. plantarum induced a more rapid and intense activation of MAPKs, especially of ERK, than L. casei. A selective blockade of ERK activation induced by L plantarum resulted in a decrease in IL-10 production and a simultaneous increase in IL-12 production. Interestingly, when macrophages were stimulated with a combination of L. plantarum and L. casei, IL-10 production was induced synergistically. We identified cell wall teichoic acid and lipoteichoic acid as key factors for triggering the synergistic induction of IL-10 production, although these teichoic acids alone only weakly induced IL-10 production. The effect of these teichoic acids on IL-10 production was mediated by TLR2-dependent ERK activation. Our data demonstrate that activation of the ERK pathway is critical for determination of the balance of the IL-10AL-12 response of macrophages to lactobacilli and that predominant IL-12 production induced by certain lactobacilli such as L. casei can be converted into predominant IL-10 production when stimulated in the presence of teichoic acids. The Journal of Immunology, 2010, 184: 3505-3513.