Prostaglandin E2 Regulates Activation of Mouse Peritoneal Macrophages by Staphylococcus aureus through Toll-Like Receptor 2, Toll-Like Receptor 4, and NLRP3 Inflammasome Signaling
Prostaglandin E2 Regulates Activation of Mouse Peritoneal Macrophages by Staphylococcus aureus through Toll-Like Receptor 2, Toll-Like Receptor 4, and NLRP3 Inflammasome Signaling
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前列腺素 E2 通过 Toll 样受体 2、Toll 样受体 4 和 NLRP3 炎性体信号传导，调节金黄色葡萄球菌对小鼠腹膜巨噬细胞的激活。
DOI：
10.1159/000499604
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发表时间：
2020-02-01
影响因子：
5.3
通讯作者：
Cao, Jinshan
中科院分区：
文献类型：
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作者：
Wu, Jindi;Liu, Bo;Cao, Jinshan
前列腺素E-2 （PGE(2)）是正常生理功能必需的内源性脂质介质，在病理条件下也可以作为炎症介质。我们确定了金黄色葡萄球菌脂蛋白是否对诱导免疫细胞分泌PGE(2)至关重要，以及模式识别受体是否介导了这一过程。与野生型（WT）金黄色葡萄球菌感染的巨噬细胞相比，感染金黄色葡萄球菌等基因突变体lgt::ermB （δ lgt；缺乏脂蛋白成熟）的小鼠腹腔巨噬细胞分泌的PGE(2)水平降低。对toll样受体2 （TLR2）缺陷、tlr4缺陷和nlrp3缺陷小鼠的实验表明，这3种蛋白参与了巨噬细胞对金黄色葡萄球菌的反应中PGE(2)的分泌，而脂蛋白是金黄色葡萄球菌在巨噬细胞内侵袭和存活所必需的。抑制内源性PGE(2)合成对细菌侵袭无影响。外源性PGE(2)抑制了金黄色葡萄球菌及其等基因突变体的吞噬作用，但增加了细胞内杀伤，同时增加了IL-1 β的分泌。我们的数据表明，金黄色葡萄球菌可以诱导巨噬细胞TLR/丝裂原活化蛋白激酶/NF-kappa B信号通路，PGE(2)处理上调NLRP3/caspase-1信号通路的激活。因此，金黄色葡萄球菌感染后巨噬细胞PGE(2)的分泌取决于细菌脂蛋白成熟和巨噬细胞受体TLR2、TLR4和NLRP3。此外，外源性PGE(2)通过TLRs和NLRP3炎性体信号传导调节金黄色葡萄球菌诱导的巨噬细胞活化。
Prostaglandin E-2 (PGE(2)), an essential endogenous lipid mediator for normal physiological functions, can also act as an inflammatory mediator in pathological conditions. We determined whether Staphylococcus aureus lipoproteins are essential for inducing PGE(2) secretion by immune cells and whether pattern recognition receptors mediate this process. PGE(2) levels secreted by mouse peritoneal macrophages infected with the S. aureus isogenic mutant, lgt::ermB (Delta lgt; deficient in lipoprotein maturation), decreased compared with those from macrophages infected with wild-type (WT) S. aureus. Experiments using toll-like receptors 2 (TLR2)-deficient, TLR4-deficient, and NLRP3-deficient mice indicated that these 3 proteins are involved in macrophage PGE(2) secretion in response to S. aureus, and lipoproteins were essential for S. aureus invasion and survival within macrophages. Inhibition of endogenous PGE(2) synthesis had no effect on bacterial invasion. Exogenous PGE(2) inhibited phagocytosis in the WT S. aureus and its isogenic mutant but increased intracellular killing accompanied by enhanced IL-1 beta secretion. Our data demonstrate that S. aureus can induce macrophage TLR/mitogen-activated protein kinase/NF-kappa B signaling and that PGE(2) treatment upregulates NLRP3/caspase-1 signaling activation. Thus, macrophage PGE(2) secretion after S. aureus infection depends on bacterial lipoprotein maturation and macrophage receptors TLR2, TLR4, and NLRP3. Moreover, exogenous PGE(2) regulates S. aureus-induced macrophage activation through TLRs and NLRP3 inflammasome signaling.