Brucella suis Vaccine Strain 2 Induces Endoplasmic Reticulum Stress that Affects Intracellular Replication in Goat Trophoblast Cells In vitro.
Brucella suis Vaccine Strain 2 Induces Endoplasmic Reticulum Stress that Affects Intracellular Replication in Goat Trophoblast Cells In vitro.
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DOI：
10.3389/fcimb.2016.00019
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发表时间：
2016
影响因子：
5.7
通讯作者：
Wang A
中科院分区：
文献类型：
--
作者：
Wang X;Lin P;Li Y;Xiang C;Yin Y;Chen Z;Du Y;Zhou D;Jin Y;Wang A
据报道，布鲁氏菌会损害胎盘滋养层细胞，而胎盘滋养层细胞是布鲁氏菌与内质网（ER）联合有效复制的细胞靶点，并最终导致怀孕动物流产。然而，布鲁氏菌对滋养细胞的确切影响尚不清楚。本文研究了猪布鲁氏菌疫苗2株（b . suisse . s2）在山羊滋养细胞（GTCs）中的感染和复制，以及体外诱导的细胞和分子反应。我们的研究表明猪双歧杆菌。S2能够高滴度感染和增殖，抑制gtc的增殖并诱导内质网应激引起的细胞凋亡。Tunicamycin （Tm）是一种强烈增加内质网应激诱导的细胞凋亡的药物伴侣，可抑制猪双球菌。gtc中的S2复制。此外，4苯基丁酸（4- pba）是一种缓解内质膜应激诱导的细胞凋亡的药物伴侣，可显著增强猪b.s。gtc中的S2复制。未折叠蛋白反应（UPR）伴侣分子GRP78也促进了猪芽孢杆菌。抑制内质网应激诱导的细胞凋亡在gtc中的S2增殖。我们还发现IRE1通路，而不是PERK或ATF6通路，在这个过程中被激活。然而，Irestatin 9389 （IRE1拮抗剂）在gtc中降低磷酸化IRE1α和IRE1α蛋白的表达并不影响b . swiss . s2的增殖。虽然GTC植入对B.suis无影响。S2感染后，孕酮分泌受到抑制，催乳素和雌激素分泌增加；这些影响伴随着编码关键类固醇生成酶的基因表达的变化。本研究从病原体侵袭、内质网应激和生殖内分泌等方面系统探讨了布鲁氏菌感染流产的机制。我们的发现可能为理解布鲁氏菌感染引起山羊流产的机制提供新的见解。
Brucella has been reported to impair placental trophoblasts, a cellular target where Brucella efficiently replicates in association with the endoplasmic reticulum (ER), and ultimately trigger abortion in pregnant animals. However, the precise effects of Brucella on trophoblast cells remain unclear. Here, we describe the infection and replication of Brucella suis vaccine strain 2 (B.suis.S2) in goat trophoblast cells (GTCs) and the cellular and molecular responses induced in vitro. Our studies demonstrated that B.suis.S2 was able to infect and proliferate to high titers, hamper the proliferation of GTCs and induce apoptosis due to ER stress. Tunicamycin (Tm), a pharmacological chaperone that strongly mounts ER stress-induced apoptosis, inhibited B.suis.S2 replication in GTCs. In addition, 4 phenyl butyric acid (4-PBA), a pharmacological chaperone that alleviates ER stress-induced apoptosis, significantly enhanced B.suis.S2 replication in GTCs. The Unfolded Protein Response (UPR) chaperone molecule GRP78 also promoted B.suis.S2 proliferation in GTCs by inhibiting ER stress-induced apoptosis. We also discovered that the IRE1 pathway, but not the PERK or ATF6 pathway, was activated in the process. However, decreasing the expression of phosphoIRE1α and IRE1α proteins with Irestatin 9389 (IRE1 antagonist) in GTCs did not affect the proliferation of B.suis.S2. Although GTC implantation was not affected upon B.suis.S2 infection, progesterone secretion was suppressed, and prolactin and estrogen secretion increased; these effects were accompanied by changes in the expression of genes encoding key steroidogenic enzymes. This study systematically explored the mechanisms of abortion in Brucella infection from the viewpoint of pathogen invasion, ER stress and reproductive endocrinology. Our findings may provide new insight for understanding the mechanisms involved in goat abortions caused by Brucella infection.