DataSheet_1_Resistance to Experimental Visceral Leishmaniasis in Mice Infected With Leishmania infantum Requires Batf3.pdf

Unveiling the protective immune response to visceral leishmaniasis is critical for a rational design of vaccines aimed at reducing the impact caused by this fatal, if left untreated, vector-borne disease. In this study we sought to determine the role of the basic leucine zipper transcription factor ATF-like 3 (Batf3) in the evolution of infection with Leishmania infantum, the causative agent of human visceral leishmaniasis in the Mediterranean Basin and Latin America. For that, Batf3-deficient mice in C57BL/6 background were infected with an L. infantum strain expressing the luciferase gene. Bioluminescent imaging, as well as in vitro parasite titration, demonstrated that Batf3-deficient mice were unable to control hepatic parasitosis as opposed to wild-type C57BL/6 mice. The impaired microbicide capacities of L. infantum-infected macrophages from Batf3-deficient mice mainly correlated with a reduction of parasite-specific IFN-γ production. Our results reinforce the implication of Batf3 in the generation of type 1 immunity against infectious diseases.

揭示内脏利什曼病（visceral leishmaniasis）的保护性免疫应答，对于合理设计疫苗以减轻这种若未及时治疗便会致命的虫媒传染病所带来的危害，具有至关重要的意义。本研究旨在明确碱性亮氨酸拉链转录因子ATF样3（Batf3）在婴儿利什曼原虫（Leishmania infantum）感染进程中的作用，该原虫是地中海盆地与拉丁美洲地区人类内脏利什曼病的致病病原体。为此，我们选用C57BL/6背景的Batf3缺陷小鼠，感染一株表达荧光素酶基因（luciferase gene）的婴儿利什曼原虫菌株。通过生物发光成像（bioluminescent imaging）与体外寄生虫滴定实验，我们发现与野生型C57BL/6小鼠相比，Batf3缺陷小鼠无法有效控制肝脏寄生虫载量。Batf3缺陷小鼠来源的婴儿利什曼原虫感染巨噬细胞，其受损的抗菌能力主要与寄生虫特异性干扰素-γ（IFN-γ）的产生水平下降相关。本研究结果进一步证实了Batf3在介导针对传染病的1型免疫（type 1 immunity）生成过程中的关键作用。