Immunodominant antigens that induce Th1 and Th17 responses protect mice against Helicobacter pylori infection.
Immunodominant antigens that induce Th1 and Th17 responses protect mice against Helicobacter pylori infection.
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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幽门螺杆菌感染。
DOI：
10.18632/oncotarget.23927
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发表时间：
2018-02-23
期刊：
影响因子：
--
通讯作者：
Wu C
中科院分区：
文献类型：
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作者：
Sun H;Yuan H;Tan R;Li B;Guo G;Zhang J;Jing H;Qin Y;Zhao Z;Zou Q;Wu C
幽门螺杆菌感染了世界上一半以上的人口，引起胃炎、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幽门螺杆菌疫苗在解决这一问题方面取得了很大进展，但其疗效和寿命仍有待提高。Th1和Th17细胞在胃粘膜对幽门螺杆菌的局部保护中起重要作用。此外，保护性免疫优势抗原是首选的疫苗。本研究采用分子筛色谱法将幽门螺杆菌全细胞裂解液按分子量分成30组。选择促进CD4 T细胞增殖效果最好的组，免疫评价。然后用LC-MS/MS分析详细蛋白，并在大肠杆菌中表达。选择了11个蛋白，并对其中的优势蛋白进行了验证。结果，从幽门螺杆菌全细胞中筛选出3种保护性免疫优势抗原：肌苷5′-单磷酸脱氢酶、II型柠檬酸合成酶和脲酶亚基β。其中两个（肌苷5′-单磷酸脱氢酶和II型柠檬酸合成酶）是新发现的，一个（脲酶亚基β）是先前报道的确认。与PBS对照组相比，三种抗原混合后的幽门螺杆菌定殖水平显著降低（P < 0.001）， Th1 （P < 0.001）和Th17 （P < 0.001）应答显著增强，具有较好的保护效果。因此，肌苷5′-单磷酸脱氢酶、II型柠檬酸合成酶和脲酶亚基β是诱导显性Th1和Th17反应的三种保护性抗原，以防御幽门螺杆菌感染。
Helicobacter pylori 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 Helicobacter pylori 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 Helicobacter pylori in the stomach mucosa. Additionally, protective immunodominant antigens are the preferred for a vaccine. In this work, Helicobacter pylori 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 Helicobacter pylori 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 (P < 0.001) and stronger Th1 (P < 0.001) and Th17 (P < 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 Helicobacter pylori infection.