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诱导Th1和Th17反应的免疫显性抗原可保护小鼠免受感染。

Immunodominant antigens that induce Th1 and Th17 responses protect mice against infection.

作者信息

Sun Heqiang, Yuan Hanmei, Tan Ranjing, Li Bin, Guo Gang, Zhang Jinyong, Jing Haiming, Qin Yi, Zhao Zhuo, Zou Quanming, Wu Chao

机构信息

National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.

Department of Dermatology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China.

出版信息

Oncotarget. 2018 Jan 3;9(15):12050-12063. doi: 10.18632/oncotarget.23927. eCollection 2018 Feb 23.

Abstract

has infected more than half of the world's population, causing gastritis, gastric ulcers, gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer. The oral recombinant vaccine currently used has made great progress in addressing this problem, however, its efficacy and longevity still need to be improved. Th1 and Th17 cells play essential roles in local protection against in the stomach mucosa. Additionally, protective immunodominant antigens are the preferred for a vaccine. In this work, whole cell lysate was separated into 30 groups based on molecular weight by molecular sieve chromatography. The group best promoting CD4 T cells proliferation was selected and evaluated by immunization. The detail proteins were then analyzed by LC-MS/MS and expressed in Escherichia coli. Eleven proteins were selected and the dominant ones were demonstrated. As a result, three protective immunodominant antigens, inosine 5'-monophosphate dehydrogenase, type II citrate synthase, and urease subunit beta, were selected from whole cell. Two of them (inosine 5'-monophosphate dehydrogenase and type II citrate synthase) were newly identified, and one (urease subunit beta) was confirmed as previously reported. The mixture of the three antigens showed satisfactory protective efficiency, with significant lower H. pylori colonization level ( < 0.001) and stronger Th1 ( < 0.001) and Th17 ( < 0.001) responses than PBS control group. Thus, inosine 5'-monophosphate dehydrogenase, type II citrate synthase, and urease subunit beta are three protective antigens inducing dominant Th1 and Th17 responses to defend against infection.

摘要

已感染全球半数以上人口,引发胃炎、胃溃疡、胃黏膜相关淋巴组织淋巴瘤和胃癌。目前使用的口服重组疫苗在解决这一问题上已取得很大进展,然而,其疗效和持久性仍有待提高。Th1和Th17细胞在胃黏膜局部抵御幽门螺杆菌感染中发挥着重要作用。此外,保护性免疫显性抗原是疫苗的首选。在这项工作中,通过分子筛色谱法将全细胞裂解物按分子量分为30组。选择促进CD4 T细胞增殖最佳的组并通过免疫进行评估。然后通过液相色谱-串联质谱法分析具体蛋白质并在大肠杆菌中表达。选择了11种蛋白质并确定了其中的显性蛋白质。结果,从全细胞中筛选出三种保护性免疫显性抗原,即5'-肌苷单磷酸脱氢酶、II型柠檬酸合酶和脲酶亚基β。其中两种(5'-肌苷单磷酸脱氢酶和II型柠檬酸合酶)是新发现的,一种(脲酶亚基β)如先前报道已得到确认。这三种抗原的混合物显示出令人满意的保护效率,与PBS对照组相比,幽门螺杆菌定植水平显著降低(<0.001),Th1(<0.001)和Th17(<0.001)反应更强。因此,5'-肌苷单磷酸脱氢酶、II型柠檬酸合酶和脲酶亚基β是三种诱导显性Th1和Th17反应以抵御幽门螺杆菌感染的保护性抗原。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4580/5844728/2b7a3a6911b3/oncotarget-09-12050-g001.jpg

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