A live diarrheal vaccine imprints a Th2 cell bias and acts as an anti-inflammatory vaccine
A live diarrheal vaccine imprints a Th2 cell bias and acts as an anti-inflammatory vaccine
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DOI：
10.4049/jimmunol.175.10.6733
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发表时间：
2005-11-15
影响因子：
4.4
通讯作者：
Pascual, DW
中科院分区：
文献类型：
--
作者：
Jun, SM;Gilmore, W;Pascual, DW
一种针对产肠毒素大肠杆菌 (ETEC) 的实验性疫苗由表达产肠毒素大肠杆菌菌毛的活减毒沙门氏菌载体、定植因子 Ag I (CFA/I) 组成，口服时可刺激双相 Th 细胞反应，并抑制正常产生的促炎反应。这种抑制在沙门氏菌-CFA/I感染巨噬细胞时也很明显，导致TNF-α、IL-1和IL-6的产生减少，这表明沙门氏菌的CFA/I菌毛表达可以预防促炎性疾病。为了检验这一假设，在使用致脑炎蛋白脂质蛋白肽 PLP139-151 诱导实验性自身免疫性脑脊髓炎之前 1 或 4 周，对 SJL/J 小鼠接种沙门氏菌-CFA/I 构建体。接受沙门氏菌-CFA/I 疫苗的小鼠从轻度急性临床疾病中完全康复，并且在脊髓白质和灰质中仅表现出轻度炎症浸润。这种保护作用伴随着致脑炎性 IFN-γ 分泌 Th 细胞的丧失，并被 IL-4、IL-10 和 IL-13 分泌的增加所取代。总的来说，这些数据表明 Sahnonella-CFA/I 是一种抗炎疫苗，可下调促炎细胞并通过免疫偏差提供针对促炎性疾病（实验性自身免疫性脑脊髓炎）的保护。
An experimental vaccine for enterotoxigenic Escherichia coli (ETEC) composed of a live, attenuated Salmonella vector-expressing enterotoxigenic E. coli fimbriae, colonization factor Ag I (CFA/I), stimulated a biphasic Th cell response when given orally and suppressed the normally produced proinflammatory response. Such suppression was also evident upon the Sallnonella-CFA/I infection of macrophages resulting in diminished TNF-alpha, IL-1, and IL-6 production and suggesting that the CFA/I fimbrial expression by Salmonella may protect against a proinflammatory disease. To test this hypothesis, SJL/J mice were vaccinated with Salmonella-CFA/I construct 1 or 4 wk before induction of experimental autoimmune encephalomyelitis using an encephalitogenic proteolipid protein peptide, PLP139-151. Mice receiving Salmonella-CFA/I vaccine recovered completely from mild acute clinical disease and showed only mild inflammatory infiltrates in the spinal cord white and gray matter. This protective effect was accompanied by a loss of encephalitogenic IFN-gamma-secreting Th cells and was replaced with an increase in IL-4, IL-10, and IL-13 secretion. Collectively, these data suggested that Sahnonella-CFA/I is an anti-inflammatory vaccine that down-regulates proinflammatory cells and confers protection against a proinflammatory disease, experimental autoimmune encephalomyelitis, via immune deviation.