Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection.
Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection.
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DOI：
10.1016/j.immuni.2016.06.002
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发表时间：
2016-06-21
期刊：
影响因子：
32.4
通讯作者：
McKimmie CS
中科院分区：
文献类型：
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作者：
Pingen M;Bryden SR;Pondeville E;Schnettler E;Kohl A;Merits A;Fazakerley JK;Graham GJ;McKimmie CS
埃及伊蚊负责传播许多医学上重要的病毒，如引起寨卡和登革热的病毒。将病毒接种到蚊子叮咬部位是所有蚊媒病毒感染的重要和常见阶段。我们表明，使用Semliki森林病毒和Bunyamwera病毒，这些病毒使用这种炎症生态位，以帮助他们在体内的复制和传播。蜱虫叮咬的特征是水肿，保留在接种部位的病毒和中性粒细胞的炎性流入，协调局部先天免疫程序，无意中促进病毒感染，通过鼓励病毒允许的骨髓细胞的进入和感染。中性粒细胞耗竭和炎性小体活性的治疗性阻断抑制了炎症，并消除了叮咬促进感染的能力。这项研究确定了蚊子叮咬炎症的各个方面，这些方面是病毒感染的后续全身过程和临床结果的重要决定因素。蚊虫叮咬增强病毒复制和传播并增加宿主死亡率嗜中性粒细胞驱动的炎症将病毒保留在皮肤中以驱动巨噬细胞募集募集和驻留的骨髓细胞被感染并复制病毒阻断白细胞募集到叮咬部位抑制病毒感染将病毒接种到蚊虫叮咬部位是虫媒病毒感染的重要和常见阶段。McKimmie及其同事表明，叮咬部位的炎症有助于病毒在体内复制和传播，导致更严重的感染。这些发现定义了暴露后预防性干预的其他目标。
Aedes aegypti mosquitoes are responsible for transmitting many medically important viruses such as those that cause Zika and dengue. The inoculation of viruses into mosquito bite sites is an important and common stage of all mosquito-borne virus infections. We show, using Semliki Forest virus and Bunyamwera virus, that these viruses use this inflammatory niche to aid their replication and dissemination in vivo. Mosquito bites were characterized by an edema that retained virus at the inoculation site and an inflammatory influx of neutrophils that coordinated a localized innate immune program that inadvertently facilitated virus infection by encouraging the entry and infection of virus-permissive myeloid cells. Neutrophil depletion and therapeutic blockade of inflammasome activity suppressed inflammation and abrogated the ability of the bite to promote infection. This study identifies facets of mosquito bite inflammation that are important determinants of the subsequent systemic course and clinical outcome of virus infection. Mosquito bites enhance virus replication and dissemination and increase host mortality Neutrophil-driven inflammation retains virus in skin to drive macrophage recruitment Recruited and resident myeloid cells become infected and replicate virus Blocking leukocyte recruitment to bite site inhibits viral infection The inoculation of viruses into mosquito bite sites is an important and common stage of arbovirus infections. McKimmie and colleagues show that inflammation at bite sites aids viral replication and dissemination in vivo, resulting in more severe infection. These findings define additional targets for post-exposure prophylactic intervention.