Department of Parasitology and Infectious Diseases, Gifu University Graduate School of Medicine, Gifu, Japan; Office of Academic Affairs, Faculty of Veterinary Sciences, Mahasarakham University, Mahasarakham, Thailand.
Department of Parasitology and Infectious Diseases, Gifu University Graduate School of Medicine, Gifu, Japan.
Biochem Biophys Res Commun. 2018 Nov 17;506(1):20-26. doi: 10.1016/j.bbrc.2018.10.055. Epub 2018 Oct 15.
Visceral leishmaniasis, the most severe form of leishmaniasis, is caused by Leishmania donovani and L. infantum. Immunity to Leishmania infection 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 to L. donovani infection, 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 pathway in vivo by 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 against L. donovani infection by elevating IFN-γ-independent NADPH oxidase activity, and also that cIgs play a regulatory role in controlling L. donovani infection in mice.
内脏利什曼病是最严重的利什曼病形式，由杜氏利什曼原虫和婴儿利什曼原虫引起。已经表明，对利什曼原虫感染的免疫依赖于 Th1 细胞的发育；然而，B 细胞和抗体在感染过程中的作用仍不清楚。在本研究中，我们表明，AID 和 μs 双重缺陷小鼠（DKO）具有 B 细胞但没有循环免疫球蛋白（cIgs），对杜氏利什曼原虫感染具有抗性，而 μs 或 AID 单一缺陷小鼠则没有。这种在 DKO 小鼠中的抗性发生在感染的早期阶段的肝脏中。IFN-γ 的耗竭并不影响寄生虫负荷的快速减少，而 NADPH 氧化酶在感染的 DKO 小鼠的肝脏中被上调。体内 NADPH 氧化酶抑制剂 apocynin 抑制活性氧途径导致 DKO 小鼠中的寄生虫负荷显著增加。这些结果表明，循环 Ig 缺乏通过提高 IFN-γ 非依赖性 NADPH 氧化酶活性诱导针对杜氏利什曼原虫感染的保护反应，并且 cIgs 在控制小鼠中的杜氏利什曼原虫感染中发挥调节作用。
