The circulating immunoglobulins negatively impact on the parasite clearance in the liver of Leishmania donovani-infected mice via dampening ROS activity
The circulating immunoglobulins negatively impact on the parasite clearance in the liver of Leishmania donovani-infected mice via dampening ROS activity
复制标题
循环免疫球蛋白通过抑制 ROS 活性对杜氏利什曼原虫感染小鼠肝脏中的寄生虫清除产生负面影响
DOI：
10.1016/j.bbrc.2018.10.055
复制
发表时间：
2018
影响因子：
3.1
通讯作者：
Maekawa Yoichi
中科院分区：
文献类型：
--
作者：
Srinontong Piyarat;Wu Zhiliang;Sato Katsuya;Nagaoka Hitoshi;Maekawa Yoichi
内脏利什曼病是利什曼病最严重的形式，由多诺瓦利什曼原虫和l。infantum。对利什曼感染的免疫已被证明依赖于Th1细胞的发育；然而，B细胞和抗体在感染过程中的作用尚不清楚。在本研究中，我们发现AID和μs双缺陷小鼠（DKO）具有B细胞，但没有循环免疫球蛋白（cIgs），对toL产生抗性。而μs或AID单缺陷小鼠则没有。DKO小鼠的这种耐药发生在感染早期的肝脏中。IFN-γ的消耗不影响寄生虫负荷的快速减少，而NADPH氧化酶在感染DKO小鼠的肝脏中上调。NADPH氧化酶抑制剂罗布麻苷抑制体内活性氧途径，导致DKO小鼠寄生虫负担显著增加。这些结果表明，循环Ig缺乏诱导了对l的保护性反应。通过提高IFN-γ不依赖的NADPH氧化酶活性，以及cIgs在控制l中发挥调节作用。小鼠donovani感染。
Visceral leishmaniasis, the most severe form of leishmaniasis, is caused by Leishmania donovani andL. infantum. Immunity toLeishmaniainfection has been shown to depend on the development of Th1 cells; however, the roles of B cells and antibodies during infection remain unclear. In the present study, we showed that AID and μs double-deficient mice (DKO), which have B cells but not circulating immunoglobulins (cIgs), became resistant toL. donovaniinfection, whereas μs or AID single-deficient mice did not. This resistance in DKO mice occurred in the liver from an early stage of the infection. The depletion of IFN-γ did not affect the rapid reduction of parasite burden, whereas NADPH oxidases was up-regulated in the livers of infected DKO mice. The inhibition of the reactive oxygen species pathwayin vivoby apocynin, a NADPH oxidase inhibitor, resulted in a significant increase in the parasite burden in DKO mice. These results indicate that a circulating Ig deficiency induces a protective response againstL. donovaniinfection by elevating IFN-γ-independent NADPH oxidase activity, and also that cIgs play a regulatory role in controllingL. donovaniinfection in mice.