Malaria parasite induces tryptophan-related immune suppression in mice
Malaria parasite induces tryptophan-related immune suppression in mice
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DOI：
10.1017/s0031182007002326
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发表时间：
2007-07-01
期刊：
影响因子：
2.4
通讯作者：
Himeno, K.
中科院分区：
文献类型：
--
作者：
Tetsutani, K.;To, H.;Himeno, K.
疟原虫属导致人类最严重的寄生虫病，并以复杂的方式逃避宿主免疫。树突状细胞中色氨酸的活化催化剂被认为抑制免疫，这是由色氨酸催化剂的诱导性限速酶吲哚胺2，3双加氧酶（IDO）介导的，通过色氨酸消耗和毒性代谢产物的产生。在包括疟疾在内的各种感染中，已知IDO被激活，但其生物学意义尚不清楚;因此，我们研究了疟疾寄生虫是否诱导IDO来抑制宿主免疫反应。我们发现IDO的酶活性在我们的小鼠疟疾模型中系统地升高，并且通过用1-甲基色氨酸进行体内IDO抑制而被消除。实验感染约氏疟原虫表明，IDO抑制轻微抑制寄生虫密度与增强的增殖和IFN-γ产生的CD 4（+）T细胞响应疟疾寄生虫。我们的观察表明，诱导IDO是疟原虫的免疫机制之一。
Plasmodium spp. cause the worst parasitic diseases in humans and evade host immunity in complicated ways. Activated catabolism of tryptophan in dendritic cells is thought to suppress immunity, which is mediated by an inducible rate-limiting enzyme of tryptophan catabolism, indolearnine 2,3 dioxygenase (IDO), via both tryptophan depletion and production of toxic metabolites. In various infections, including malaria, IDO is known to be activated but its biological significance is unclear;, therefore, we investigated whether malaria parasites induce IDO to suppress host immune responses. We found that enzymatic activity of IDO was elevated systematically in our mouse malaria model, and was abolished by in vivo IDO inhibition with 1-methyl tryptophan. Experimental infection with Plasmodium yoelii showed that IDO inhibition slightly suppressed parasite density in association with enhanced proliferation and IFN-y production by CD4(+) T cells in response to malaria parasites. Our observations suggest that induction of IDO is one of the immune mechanisms of malaria parasites.