Wagemakers Alex, Coumou Jeroen, Schuijt Tim J, Oei Anneke, Nijhof Ard M, van 't Veer Cornelis, van der Poll Tom, Bins Adriaan D, Hovius Joppe W R
1 Center for Experimental and Molecular Medicine, Academic Medical Center , Amsterdam, the Netherlands .
2 Department of Medical Microbiology, Academic Medical Center , Amsterdam, the Netherlands .
Vector Borne Zoonotic Dis. 2016 Apr;16(4):223-8. doi: 10.1089/vbz.2015.1901. Epub 2016 Feb 22.
We previously identified tick salivary lectin pathway inhibitor (TSLPI) in Ixodes scapularis, a vector for Borrelia burgdorferi sensu stricto (s.s.) in North America. TSLPI is a salivary protein facilitating B. burgdorferi s.s. transmission and acquisition by inhibiting the host lectin complement pathway through interference with mannose binding lectin (MBL) activity. Since Ixodes ricinus is the predominant vector for Lyme borreliosis in Europe and transmits several complement sensitive B. burgdorferi sensu lato (s.l.) strains, we aimed to identify, describe, and characterize the I. ricinus ortholog of TSLPI.
We performed (q)PCRs on I. ricinus salivary gland cDNA to identify a TSLPI ortholog. Next, we generated recombinant (r)TSLPI in a Drosophila expression system and examined inhibition of the MBL complement pathway and complement-mediated killing of B. burgdorferi s.l. in vitro.
We identified a TSLPI ortholog in I. ricinus salivary glands with 93% homology at the RNA and 89% at the protein level compared to I. scapularis TSLPI, which was upregulated during tick feeding. In silico analysis revealed that TSLPI appears to be part of a larger family of Ixodes salivary proteins among which I. persulcatus basic tail salivary proteins and I. scapularis TSLPI and Salp14. I. ricinus rTSLPI inhibited the MBL complement pathway and protected B. burgdorferi s.s. and Borrelia garinii from complement-mediated killing.
We have identified a TSLPI ortholog, which protects B. burgdorferi s.l. from complement-mediated killing in I. ricinus, the major vector for tick-borne diseases in Europe.
我们之前在肩突硬蜱中鉴定出蜱唾液凝集素途径抑制剂(TSLPI),肩突硬蜱是北美莱姆病螺旋体狭义种(Borrelia burgdorferi sensu stricto,s.s.)的传播媒介。TSLPI是一种唾液蛋白,通过干扰甘露糖结合凝集素(MBL)活性来抑制宿主凝集素补体途径,从而促进莱姆病螺旋体狭义种的传播和获取。由于蓖麻硬蜱是欧洲莱姆病的主要传播媒介,并传播几种对补体敏感的广义种莱姆病螺旋体(Borrelia burgdorferi sensu lato,s.l.)菌株,我们旨在鉴定、描述和表征蓖麻硬蜱中TSLPI的直系同源物。
我们对蓖麻硬蜱唾液腺cDNA进行(定量)PCR,以鉴定TSLPI的直系同源物。接下来,我们在果蝇表达系统中生成重组(r)TSLPI,并在体外检测其对MBL补体途径的抑制作用以及补体介导的对广义种莱姆病螺旋体的杀伤作用。
我们在蓖麻硬蜱唾液腺中鉴定出一种TSLPI直系同源物,与肩突硬蜱TSLPI相比,其RNA水平同源性为93%,蛋白质水平同源性为89%,且在蜱进食过程中上调。计算机分析表明,TSLPI似乎是硬蜱唾液蛋白大家族的一部分,其中包括全沟硬蜱碱性尾部唾液蛋白、肩突硬蜱TSLPI和Salp14。蓖麻硬蜱rTSLPI抑制了MBL补体途径,并保护狭义种莱姆病螺旋体和伽氏疏螺旋体免受补体介导的杀伤。
我们鉴定出一种TSLPI直系同源物,它能保护广义种莱姆病螺旋体在欧洲蜱传疾病的主要传播媒介蓖麻硬蜱中免受补体介导的杀伤。