Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the lyme disease agent.
Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the lyme disease agent.
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DOI：
10.1371/journal.ppat.1001205
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发表时间：
2010-11-24
期刊：
影响因子：
6.7
通讯作者：
Fikrig E
中科院分区：
文献类型：
--
作者：
Dai J;Narasimhan S;Zhang L;Liu L;Wang P;Fikrig E
扁虱广泛分布于世界各地，通过传播多种病原体影响人类和动物的健康。目前还没有针对大多数壁虱传播病原体的有效疫苗。在这项研究中，我们鉴定了来自肩部硬蜱的硬蜱组胺释放因子(THRF)，并讨论了该抗原在硬蜱充血和伯氏硬蜱传播的背景下的疫苗潜力。免疫印迹和定量逆转录-聚合酶链式反应结果表明，tHRF在硬体唾液中分泌，在感染伯氏疏螺旋体的硬体中表达上调。此外，tHRF的表达与硬蜱的快速摄食阶段一致，表明tHRF在硬蜱充血过程中起到了作用，同时也促进了伯氏假丝虫的有效传播。通过RNA干扰(RNAi)沉默tHRF显著降低了小鼠的摄食和伯氏杆菌的载量。用重组tHRF主动免疫小鼠或被动转移tHRF抗血清来干扰tHRF，也能显著降低小鼠的摄食效率和伯氏杆菌的载量。重组tHRF能与宿主嗜碱性粒细胞结合并刺激组胺释放。因此，我们推测tHRF可能在体内发挥作用，调节血管通透性，增加流向扁虱咬伤部位的血流量，促进扁虱的充血。这些发现表明，阻断tHRF可能提供一种可行的战略，以补充正在进行的开发疫苗的努力，以阻断蜱传病原体的喂养和传播。扁虱广泛分布于世界各地，通过传播多种病原体影响人类和动物的健康。目前还没有针对大多数壁虱传播病原体的安全有效的疫苗。典型的疫苗直接针对微生物，使用有机体的提取物或重组抗原作为免疫原；从理论上讲，也可以通过干扰壁虱以哺乳动物宿主为食的能力来防止壁虱传播病原体。在这项研究中，我们表征了一种推定的组胺释放因子(THRF)，它是北美莱姆病病原体伯氏杆菌的主要媒介。我们的结果表明，tHRF存在于硬蜱的唾液中，对硬蜱的摄食至关重要；阻断tHRF显著降低了硬蜱的摄食效率，并降低了小鼠体内伯氏杆菌的负担。这一发现为扁虱饲养的分子机制提供了新的见解，并提供了一种潜在的疫苗靶标来阻止扁虱饲养和病原体传播。
Ticks are distributed worldwide and affect human and animal health by transmitting diverse infectious agents. Effective vaccines against most tick-borne pathogens are not currently available. In this study, we characterized a tick histamine release factor (tHRF) from Ixodes scapularis and addressed the vaccine potential of this antigen in the context of tick engorgement and B. burgdorferi transmission. Results from western blotting and quantitative Reverse Transcription-PCR showed that tHRF is secreted in tick saliva, and upregulated in Borrelia burgdorferi-infected ticks. Further, the expression of tHRF was coincident with the rapid feeding phase of the tick, suggesting a role for tHRF in tick engorgement and concomitantly, for efficient B. burgdorferi transmission. Silencing tHRF by RNA interference (RNAi) significantly impaired tick feeding and decreased B. burgdorferi burden in mice. Interfering with tHRF by actively immunizing mice with recombinant tHRF, or passively transferring tHRF antiserum, also markedly reduced the efficiency of tick feeding and B. burgdorferi burden in mice. Recombinant tHRF was able to bind to host basophils and stimulate histamine release. Therefore, we speculate that tHRF might function in vivo to modulate vascular permeability and increase blood flow to the tick bite-site, facilitating tick engorgement. These findings suggest that blocking tHRF might offer a viable strategy to complement ongoing efforts to develop vaccines to block tick feeding and transmission of tick-borne pathogens. Ticks are distributed worldwide and affect human and animal health by transmitting diverse infectious agents. Safe and effective vaccines against most tick-borne pathogens are not currently available. Typical vaccines target microbes directly, using extracts of the organism, or recombinant antigens as the immunogen; the transmission of tick-borne pathogens can also theoretically be prevented by interfering with the ability of ticks to feed on a mammalian host. In this study, we have characterized a putative histamine release factor (tHRF) from I. scapularis ticks, the predominant vector of B. burgdorferi, the agent of Lyme disease in North America. Our results suggested that tHRF is presented in tick saliva and critical for tick feeding; blocking tHRF markedly reduced the efficiency of tick feeding, and reduced the B. burgdorferi burden in mice. This finding provides novel insights into the molecular mechanisms of tick feeding and provides a potential vaccine target to block tick feeding and pathogen transmission.
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影响因子：
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作者：
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