A novel sphingomyelinase-like enzyme in Ixodes scapularis tick saliva drives host CD4 T cells to express IL-4.
A novel sphingomyelinase-like enzyme in Ixodes scapularis tick saliva drives host CD4 T cells to express IL-4.
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DOI：
10.1111/j.1365-3024.2009.01095.x
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发表时间：
2009-04
影响因子：
2.2
通讯作者：
Wikel SK
中科院分区：
文献类型：
--
作者：
Alarcon-Chaidez FJ;Boppana VD;Hagymasi AT;Adler AJ;Wikel SK
蜱虫摄食调节宿主免疫反应。蜱诱导宿主CD4+ T细胞向Th2细胞因子倾斜，促进了蜱传病原体的传播，否则这些病原体将被Th1细胞因子中和。tick衍生的驱动Th2反应的因素以前没有被描述过。本研究对采食18-24小时制备的肩胛骨蜱cDNA文库进行了检测，鉴定并表达了一个与Loxosceles蜘蛛毒液蛋白同源的具有鞘磷脂酶活性的蜱基因。这种肩胛骨鞘磷脂酶样（IsSMase）蛋白是一种依赖于Mg+2的中性（pH 7.4）鞘磷脂酶。值得注意的是，在体内TCR转基因过继转移实验中，IsSMase编程宿主CD4+ T细胞表达标志性的Th2效应细胞因子IL-4。IsSMase似乎直接编程宿主CD4 T细胞IL-4表达（而不是其代谢副产物），因为当酶活性被中和时，诱导的IL-4表达不会改变。IsSMase也显著提高了TCR转基因CD4 T细胞的增殖（cfse稀释）。此外，IsSMase将Th2反应叠加到病毒引发的Th1反应上。因此，IsSMase是第一个能够编程宿主CD4+ T细胞表达IL-4的蜱虫分子。
Tick feeding modulates host immune responses. Tick-induced skewing of host CD4+ T cells towards a Th2 cytokine profile facilitates transmission of tick-borne pathogens that would otherwise be neutralized by Th1 cytokines. Tick-derived factors that drive this Th2 response have not previously been characterized. In the current study, we examined an I. scapularis cDNA library prepared at 18-24 hours of feeding and identified and expressed a tick gene with homology to Loxosceles spider venom proteins with sphingomyelinase activity. This I. scapularis sphingomyelinase-like (IsSMase) protein is a Mg+2-dependent, neutral (pH 7.4) form of sphingomyelinase. Significantly, in an in vivo TCR transgenic adoptive transfer assay IsSMase programmed host CD4+ T cells to express the hallmark Th2 effector cytokine IL-4. IsSMase appears to directly program host CD4 T cell IL-4 expression (as opposed to its metabolic by-products) because induced IL-4 expression was not altered when enzymatic activity was neutralized. TCR transgenic CD4 T cell proliferation (CFSE-dilution) was also significantly increased by IsSMase. Furthermore, a Th2 response is superimposed onto a virally-primed Th1 response by IsSMase. Thus, IsSMase is the first identified tick molecule capable of programming host CD4+ T cells to express IL-4.
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影响因子：
1.3
作者：
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通讯作者：
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影响因子：
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