Host skin immunity to arthropod vector bites: from mice to humans

Joshua R. Lacsina, Ryan Kissinger, Johannes S. P. Doehl, Maria Disotuar, George Petrellis, Mara Short, Elliot Lowe, James Oristian, Daniel Sonenshine, Thiago DeSouza-Vieira
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Abstract

Infections caused by vector-borne pathogens impose a significant burden of morbidity and mortality in a global scale. In their quest for blood, hematophagous arthropods penetrate the host skin and may transmit pathogens by the bite. These pathogens are deposited along with saliva and a complex mixture of vector derived factors. Hematophagous arthopod vectors have evolved a complex array of adaptations to modulate the host immune response at the bite site with the primary goal to improve blood feeding, which have been exploited throughout evolution by these pathogens to enhance infection establishment in the host. While this paradigm has been firmly established in mouse models, comparable data from human studies are scarce. Here we review how the host skin immune response to vector bites in animal models is hijacked by microbes to promote their pathogenesis. We mainly explored four distinct vector-pathogen pairs of global health importance: sand flies and Leishmania parasites, Ixodes scapularis ticks and Borrelia burgdorferi, Aedes aegypti mosquitoes and arboviruses, and Anopheles gambiae mosquitos and Plasmodium parasites. Finally, we outline how critical it is for the field of vector biology to shift from rodent models to clinical studies focused on the interface of vector-pathogen-host immune system to push further the frontiers of knowledge of the field.
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宿主皮肤对节肢动物媒介叮咬的免疫力:从小鼠到人类
病媒传播的病原体引起的感染在全球范围内造成了严重的发病率和死亡率。噬血节肢动物在觅血过程中会穿透宿主的皮肤,并通过叮咬传播病原体。这些病原体与唾液和病媒衍生因子的复杂混合物一起沉积。嗜血节肢动物载体已经进化出一系列复杂的适应性,可以在叮咬部位调节宿主的免疫反应,其主要目的是改善吸血,这些病原体在进化过程中一直在利用这些适应性来加强在宿主体内的感染。虽然这一模式已在小鼠模型中牢固确立,但来自人类研究的可比数据却很少。在此,我们回顾了在动物模型中宿主皮肤对病媒叮咬的免疫反应是如何被微生物劫持以促进其致病的。我们主要探讨了对全球健康具有重要意义的四对不同的病媒-病原体:沙蝇和利什曼原虫、蜱和博氏杆菌、埃及伊蚊和虫媒病毒以及冈比亚按蚊和疟原虫。最后,我们概述了病媒生物学领域从啮齿动物模型转向以病媒-病原体-宿主免疫系统界面为重点的临床研究对于进一步推动该领域知识前沿的重要性。
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