Arthropod-Borne Animal Diseases Research Unit, Agricultural Research Service, US Department of Agriculture, Manhattan, KS, 66502, USA.
Southeastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.
Parasit Vectors. 2018 Jun 20;11(1):358. doi: 10.1186/s13071-018-2935-0.
Hematophagous Culicoides spp. biting midges are of great agricultural importance as livestock, equine, and wildlife pests and as vectors of the orbiviruses bluetongue, epizootic hemorrhagic disease and African horse sickness. To obtain a blood meal, midges deposit saliva containing allergens, proteases, and anti-hemostatic factors, into the dermis to facilitate feeding. Infected midges deposit virus along with the myriad of salivary proteins during feeding. The extreme efficiency with which midges are able to transmit orbiviruses is not clearly understood, as much is still unknown about the physiological trauma of the bite and immune responses to saliva deposited during feeding. Of particular interest are the first few hours and days after the bite; a critical time period for any midge-transmitted virus to quickly establish a localized infection and disseminate, while avoiding the hosts' immune responses.
A mouse-midge feeding model using colonized Culicoides sonorensis midges was used to characterize innate mammalian immune responses to blood-feeding. Histological analysis of skin, and cellular and cytokine profiles of draining lymph nodes show Culicoides midge feeding elicited a potent pro-inflammatory Th-mediated cellular response with significant mast cell activation, subcutaneous hematomas, hypodermal edema and dermal capillary vasodilation, and rapid infiltration of leukocytes to the bite sites. Mast cell degranulation, triggered by bite trauma and specifically by midge saliva, was key to physiological and immunological responses and the ability of midges to feed to repletion.
Midge feeding causes physiological and immunological responses that would be highly favorable for rapid infection and systemic dissemination orbiviruses if delivered during blood-feeding. Recruitment of leukocytic cells to bitten skin brings susceptible cell populations in proximity of deposited virus within hours of feeding. Infected cells would drain to lymph nodes, which become hyperplastic in response to saliva, and result in robust viral replication in expanding cell populations and dissemination via the lymph system. Additionally, saliva-induced vasodilation and direct breaches in dermal capillaries by biting mouthparts exposes susceptible vascular endothelial cells, thereby providing immediate sites of virus replication and a dissemination route via the circulatory system. This research provides insights into the efficiency of Culicoides midges as orbivirus vectors.
吸血性库蠓属（Culicoides）的蠓叮咬媒介对畜牧业、马科动物和野生动物具有重要的危害性，是蓝舌病、传染性造血器官坏死病和非洲马瘟等环状病毒的载体。为了获得血液餐，蠓在真皮中注入含有过敏原、蛋白酶和抗凝血因子的唾液，以促进进食。感染的蠓在进食时会将病毒与无数唾液蛋白一起沉积。蠓传播环状病毒的效率极高，但我们对叮咬造成的生理创伤和进食时沉积的唾液引起的免疫反应仍知之甚少。特别值得关注的是叮咬后的头几个小时和几天；这是任何由蠓传播的病毒迅速建立局部感染并传播的关键时期，同时避免宿主的免疫反应。
使用已定植的索诺兰库蠓（Culicoides sonorensis）蠓建立了一种鼠蠓喂养模型，以描述哺乳动物对吸血的固有免疫反应。皮肤的组织学分析以及引流淋巴结的细胞和细胞因子图谱显示，库蠓的叮咬引起了强烈的促炎 Th 介导的细胞反应，伴有显著的肥大细胞活化、皮下血肿、皮下水肿和真皮毛细血管扩张，以及白细胞迅速浸润到叮咬部位。由叮咬创伤引发的肥大细胞脱颗粒，特别是由蠓唾液引发的脱颗粒，是生理和免疫反应的关键，也是蠓能够吸血至饱的关键。
如果在吸血期间传播，蠓的吸血会引起生理和免疫反应，这对快速感染和环状病毒的全身传播非常有利。白细胞细胞募集到受叮咬的皮肤，将易感细胞群在进食后数小时内带到沉积的病毒附近。受感染的细胞会引流到淋巴结，淋巴结会对唾液产生增生反应，导致复制病毒在不断扩展的细胞群中大量复制，并通过淋巴系统传播。此外，唾液引起的血管扩张和叮咬口器直接破坏真皮毛细血管，使易感血管内皮细胞暴露，从而提供病毒复制的即时部位，并通过循环系统提供传播途径。这项研究深入了解了库蠓作为环状病毒载体的效率。
