Immunization against arthropod protein impairs transmission of rickettsial pathogen from ticks to the vertebrate host.
Immunization against arthropod protein impairs transmission of rickettsial pathogen from ticks to the vertebrate host.
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DOI：
10.1038/s41541-023-00678-y
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发表时间：
2023-05-30
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
--
作者：
由嗜吞噬细胞无形体引起的人类无形体病是美国最常见的蜱传疾病之一。黑腿蜱，肩突硬蜱，将这种细菌传播给人类。在这项研究中，我们提供的证据表明，针对I。肩胛肌膜结合的有机阴离子转运多肽4056（IsOATP 4056）与抗载体疫苗一起影响A.嗜吞噬细胞菌从蜱传播到脊椎动物宿主。嗜吞噬细胞无形体诱导蜱和蜱细胞中IsOATP 4056的表达。在A.嗜吞噬细胞菌感染的蜱细胞。靶向IsOATP 4056最大细胞外环的高剂量（10 µ g/ml）而非低剂量（5 µ g/ml）EL-6抗体处理在蜱细胞中显示出细胞毒性效应，但在人角质形成细胞系（HaCaT）中未显示出细胞毒性效应。被动免疫、蜱介导的传播和用从两个商业供应商订购的小鼠和用蜱细胞进行的体外研究表明，EL-6抗体不仅损害A.这不仅有助于嗜吞噬细胞菌从蜱传播到鼠宿主，而且还有助于通过激活节肢动物Toll途径减少饱食蜱内和蜱细胞中的细菌负荷。此外，在饲喂EL-6抗体免疫小鼠的蜱中注意到蜕皮效率降低。这些结果为研制针对A.嗜吞噬细胞菌和可能的其他具有医学重要性的蜱传病原体。
Human anaplasmosis caused by Anaplasma phagocytophilum is one of the most common tick-borne diseases in the United States. The black-legged ticks, Ixodes scapularis, vector and transmit this bacterium to humans. In this study, we provide evidence that targeting I. scapularis membrane-bound organic anion transporting polypeptide 4056 (IsOATP4056) with an anti-vector vaccine affects transmission of A. phagocytophilum from ticks to the vertebrate host. Anaplasma phagocytophilum induces expression of IsOATP4056 in ticks and tick cells. Increased membrane localization of IsOATP4056 was evident in A. phagocytophilum-infected tick cells. Treatment with high dose (10 µg/ml) but not low dose (5 µg/ml) of EL-6 antibody that targets the largest extracellular loop of IsOATP4056 showed cytotoxic effects in tick cells but not in human keratinocyte cell line (HaCaT). Passive immunization, tick-mediated transmission and in vitro studies performed with mice ordered from two commercial vendors and with tick cells showed that EL-6 antibody not only impairs A. phagocytophilum transmission from ticks to the murine host but also aids in the reduction in the bacterial loads within engorged ticks and in tick cells by activation of arthropod Toll pathway. Furthermore, reduced molting efficiency was noted in ticks fed on EL-6 antibody-immunized mice. Collectively, these results provide a good candidate for the development of anti-tick vaccine to target the transmission of A. phagocytophilum and perhaps other tick-borne pathogens of medical importance.
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影响因子：
7.8
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