Pal Utpal, Li Xin, Wang Tian, Montgomery Ruth R, Ramamoorthi Nandhini, Desilva Aravinda M, Bao Fukai, Yang Xiaofeng, Pypaert Marc, Pradhan Deepti, Kantor Fred S, Telford Sam, Anderson John F, Fikrig Erol
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Cell. 2004 Nov 12;119(4):457-68. doi: 10.1016/j.cell.2004.10.027.
The Lyme disease agent Borrelia burgdorferi naturally persists in a cycle that primarily involves ticks and mammals. We have now identified a tick receptor (TROSPA) that is required for spirochetal colonization of Ixodes scapularis. B. burgdorferi outer surface protein A, which is abundantly expressed on spirochetes within the arthropod and essential for pathogen adherence to the vector, specifically bound to TROSPA. TROSPA mRNA levels in ticks increased following spirochete infestation and decreased in response to engorgement, events that are temporally linked to B. burgdorferi entry into and egress from the vector. The blockade of TROSPA by TROSPA antisera or by the repression of TROSPA expression via RNA interference reduced B. burgdorferi adherence to the I. scapularis gut in vivo, thereby preventing efficient colonization of the vector and subsequently reducing pathogen transmission to the mammalian host. Identification of an I. scapularis receptor for B. burgdorferi is the first step toward elucidating arthropod ligands that are required for survival of spirochetes in nature.
莱姆病病原体伯氏疏螺旋体自然存在于一个主要涉及蜱虫和哺乳动物的循环中。我们现已鉴定出一种肩突硬蜱螺旋体定殖所需的蜱虫受体(TROSPA)。伯氏疏螺旋体外膜蛋白A在节肢动物体内的螺旋体上大量表达,是病原体黏附于载体所必需的,它能特异性结合TROSPA。蜱虫感染螺旋体后,TROSPA的mRNA水平升高,而饱血后则降低,这些事件在时间上与伯氏疏螺旋体进入和离开载体相关。用TROSPA抗血清阻断TROSPA或通过RNA干扰抑制TROSPA表达,可降低伯氏疏螺旋体在体内对肩突硬蜱肠道的黏附,从而阻止载体的有效定殖,并随后减少病原体向哺乳动物宿主的传播。鉴定伯氏疏螺旋体的肩突硬蜱受体是阐明自然界中螺旋体生存所需节肢动物配体的第一步。