Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Cell Host Microbe. 2018 Jan 10;23(1):134-143.e6. doi: 10.1016/j.chom.2017.12.002. Epub 2017 Dec 28.
Leishmania donovani parasites are the cause of visceral leishmaniasis and are transmitted by bites from phlebotomine sand flies. A prominent feature of vector-transmitted Leishmania is the persistence of neutrophils at bite sites, where they protect captured parasites, leading to enhanced disease. Here, we demonstrate that gut microbes from the sand fly are egested into host skin alongside Leishmania parasites. The egested microbes trigger the inflammasome, leading to a rapid production of interleukin-1β (IL-1β), which sustains neutrophil infiltration. Reducing midgut microbiota by pretreatment of Leishmania-infected sand flies with antibiotics or neutralizing the effect of IL-1β in bitten mice abrogates neutrophil recruitment. These early events are associated with impairment of parasite visceralization, indicating that both gut microbiota and IL-1β are important for the establishment of Leishmania infections. Considering that arthropods harbor a rich microbiota, its potential egestion after bites may be a shared mechanism that contributes to severity of vector-borne disease.
杜氏利什曼原虫寄生虫是内脏利什曼病的病因，通过白蛉沙蝇的叮咬传播。经媒介传播的利什曼原虫的一个显著特征是在叮咬部位持续存在中性粒细胞，它们保护捕获的寄生虫，导致疾病加重。在这里，我们证明沙蝇的肠道微生物与利什曼原虫寄生虫一起从沙蝇中排出到宿主皮肤中。排出的微生物会引发炎症小体，导致白细胞介素-1β（IL-1β）的快速产生，从而维持中性粒细胞浸润。通过用抗生素预处理感染利什曼原虫的沙蝇或中和叮咬小鼠中 IL-1β的作用来减少中肠微生物群，可以消除中性粒细胞的募集。这些早期事件与寄生虫内脏化的损害有关，表明肠道微生物群和 IL-1β 对于利什曼原虫感染的建立都是重要的。考虑到节肢动物携带着丰富的微生物群，其在叮咬后可能会排出，这可能是一种共同的机制，导致了虫媒疾病的严重程度。
