Schistosoma mansoni schistosomula antigens induce Th1/Pro-inflammatory cytokine responses.

Schistosoma mansoni schistosomula antigens induce Th1/Pro-inflammatory cytokine responses.
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曼氏血吸虫血吸虫抗原抗原诱导TH1/促炎性细胞因子反应。

DOI:
10.1111/pim.12592
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发表时间:
2018-12
影响因子:
2.2
通讯作者:
Cose S
Cose S
中科院分区:
医学4区
文献类型:
--
作者:
Egesa M;Lubyayi L;Tukahebwa EM;Bagaya BS;Chalmers IW;Wilson S;Hokke CH;Hoffmann KF;Dunne DW;Yazdanbakhsh M;Labuda LA;Cose S

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血吸虫童虫对宿主免疫反应高度敏感,是有吸引力的预防性疫苗靶点,尽管地方性人群中针对童虫抗原的细胞免疫反应尚未得到很好的表征。我们收集了54名感染曼氏血吸虫的乌干达人的血液和粪便,分离了外周血单核细胞,并用成虫和可溶性虫卵抗原(AWA和SEA)、沿着童虫重组蛋白rSmKK 7、淋巴细胞抗原6亚型(rSmLy 6A和rSmLy 6 B)、四跨膜蛋白亚型(rSmTSP 6和rSmTSP 7)刺激了它们24小时。使用多重Luminex测定法测量培养上清液中的细胞因子、趋化因子和生长因子,并使用Kato‐Katz方法测定吡喹酮(PZQ)治疗前和治疗后1年的感染强度。对细胞反应进行分组,并研究了PZQ治疗前后相关细胞反应组与感染强度之间的关系。AWA和SEA主要诱导Th 2应答。相反,rSmLy 6 B、rSmTSP 6和rSmTSP 7诱导Th 1/促炎反应。虽然重组抗原rSmKK 7和rSmLy 6A没有诱导Th 1/促炎反应,但在调整年龄和性别后,它们与治疗前感染强度相关。使用这种方法测试更多的童虫抗原可以提供优先考虑下一代血吸虫病疫苗候选物所必需的免疫流行病学标识符。
Larvae of Schistosoma (schistosomula) are highly susceptible to host immune responses and are attractive prophylactic vaccine targets, although cellular immune responses against schistosomula antigens in endemic human populations are not well characterized. We collected blood and stool from 54 Schistosoma mansoni‐infected Ugandans, isolated peripheral blood mononuclear cells and stimulated them for 24 hours with schistosome adult worm and soluble egg antigens (AWA and SEA), along with schistosomula recombinant proteins rSmKK7, Lymphocyte Antigen 6 isoforms (rSmLy6A and rSmLy6B), tetraspanin isoforms (rSmTSP6 and rSmTSP7). Cytokines, chemokines and growth factors were measured in the culture supernatants using a multiplex luminex assay, and infection intensity was determined before and at 1 year after praziquantel (PZQ) treatment using the Kato‐Katz method. Cellular responses were grouped and the relationship between groups of correlated cellular responses and infection intensity before and after PZQ treatment was investigated. AWA and SEA induced mainly Th2 responses. In contrast, rSmLy6B, rSmTSP6 and rSmTSP7 induced Th1/pro‐inflammatory responses. While recombinant antigens rSmKK7 and rSmLy6A did not induce a Th1/pro‐inflammatory response, they had an association with pre‐treatment infection intensity after adjusting for age and sex. Testing more schistosomula antigens using this approach could provide immune‐epidemiology identifiers necessary for prioritizing next generation schistosomiasis vaccine candidates.
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