Effect of <i>O</i>. <i>porcinus</i> Tick Salivary Gland Extract on the African Swine Fever Virus Infection in Domestic Pig

African swine fever is a haemorrhagic disease in pig production that can have disastrous financial consequences for farming. No vaccines are currently available and animal slaughtering or area zoning to restrict risk-related movements are the only effective measures to prevent the spread of the disease. Ornithodoros soft ticks are known to transmit the African swine fever virus (ASFV) to pigs in farms, following the natural epidemiologic cycle of the virus. Tick saliva has been shown to modulate the host physiological and immunological responses during feeding on skin, thus affecting viral infection. To better understand the interaction between soft tick, ASFV and pig at the bite location and the possible influence of tick saliva on pig infection by ASFV, salivary gland extract (SGE) of Ornithodoros porcinus, co-inoculated or not with ASFV, was used for intradermal auricular inoculation. Our results showed that, after the virus triggered the disease, pigs inoculated with virus and SGE presented greater hyperthermia than pigs inoculated with virus alone. The density of Langerhans cells was modulated at the tick bite or inoculation site, either through recruitment by ASFV or inhibition by SGE. Additionally, SGE and virus induced macrophage recruitment each. This effect was enhanced when they were co-inoculated. Finally, the co-inoculation of SGE and virus delayed the early local spread of virus to the first lymph node on the inoculation side. This study has shown that the effect of SGE was powerful enough to be quantified in pig both on the systemic and local immune response. We believe this model should be developed with infected tick and could improve knowledge of both tick vector competence and tick saliva immunomodulation.非洲猪瘟（African swine fever）是生猪养殖产业中的一类出血性疾病，可给养猪场带来灾难性的经济损失。目前尚无可用疫苗，动物扑杀与划定区域以限制风险相关移动是遏制疾病传播的唯一有效防控手段。钝缘蜱属软蜱（Ornithodoros soft ticks）可按照该病毒的自然流行病学循环，将非洲猪瘟病毒（African swine fever virus, ASFV）传播至猪场生猪。已有研究表明，蜱唾液在宿主皮肤叮咬吸血过程中可调控宿主的生理与免疫应答，进而影响病毒感染进程。为深入解析钝缘蜱、ASFV与生猪在叮咬部位的相互作用，以及蜱唾液对ASFV感染生猪的潜在影响，本研究采用猪钝缘蜱（Ornithodoros porcinus）的唾液腺提取物（salivary gland extract, SGE），分别联合或不联合ASFV进行耳内皮内接种。研究结果显示：当病毒诱发疾病后，联合接种病毒与SGE的生猪，其体温升高程度显著高于仅接种病毒的生猪；蜱叮咬或接种部位的朗格汉斯细胞密度受到调控，其机制或为ASFV介导的细胞招募，或为SGE介导的细胞抑制；此外，SGE与病毒各自均可诱导巨噬细胞招募，二者联合接种时该效应可得到增强；最后，SGE与病毒联合接种可延缓病毒早期向接种侧第一枚淋巴结的局部播散。本研究证实，SGE的效应足够显著，可在生猪体内通过系统免疫与局部免疫应答两个维度被量化检测。我们认为，该模型可结合感染钝缘蜱进行优化，从而进一步加深对蜱媒传播能力及蜱唾液免疫调控机制的认知。