Identification of Tick Ixodes ricinus Midgut Genes Differentially Expressed During the Transmission of Borrelia afzelii Spirochetes Using a Transcriptomic Approach

Lyme borreliosis is an emerging tick-borne disease caused by spirochetes Borrelia burgdorferi sensu lato. In Europe, Lyme borreliosis is predominantly caused by Borrelia afzelii and transmitted by Ixodes ricinus. Although Borrelia behavior throughout tick development is quite well documented, specific molecular interactions between Borrelia and the tick have not been satisfactorily examined. Here, we present the first transcriptomic study focused on the expression of tick midgut genes regulated by Borrelia. By using massive analysis of cDNA ends (MACE), we searched for tick transcripts expressed differentially in the midgut of unfed, 24h-fed, and fully fed I. ricinus nymphs infected with B. afzelii. In total, we identified 553 upregulated and 530 downregulated tick genes and demonstrated that B. afzelii interacts intensively with the tick. Technical and biological validations confirmed the accuracy of the transcriptome. The expression of five validated tick genes was silenced by RNA interference. Silencing of the uncharacterized protein (GXP_Contig_30818) delayed the infection progress and decreased infection prevalence in the target mice tissues. Silencing of other genes did not significantly affect tick feeding nor the transmission of B. afzelii, suggesting a possible role of these genes rather in Borrelia acquisition or persistence in ticks. Identification of genes and proteins exploited by Borrelia during transmission and establishment in a tick could help the development of novel preventive strategies for Lyme borreliosis.

Introduction

Lyme borreliosis is an emerging human disease, occurring predominantly in temperate regions of the northern hemisphere (1, 2). It is caused by spirochetes Borrelia burgdorferi sensu lato and is spread by ticks from the genus Ixodes. In Europe, ~65,000 new cases are reported annually (3). However, the real prevalence is substantially higher due to under-reporting (4). In North America, the transmission cycle primarily involves the spirochete B. burgdorferi sensu stricto and the tick Ixodes scapularis. In Europe, the disease is caused by several Borrelia species and is transmitted by related tick species, Ixodes ricinus and Ixodes persulcatus. The early disease typically manifests itself with a bulls-eye rash on the skin, called erythema migrans. The spirochetes then disseminate throughout the body to diverse tissues and are associated with arthritis, neurological symptoms, and dermatitis (5). Prompt antibiotic treatment usually cures the disease and symptoms. Despite several promising trials (6–9), a vaccine against human Lyme borreliosis is not currently available and prevention mainly depends on avoiding tick bites (10).

Mahmood S., Šíma R., Urbanová V., Trentelman J.J.A., Krezdorn N., Winter P., Kopáček P., Hovius J.W., Hajdušek O. 2021: Identification of Tick Ixodes ricinus Midgut Genes Differentially Expressed During the Transmission of Borrelia afzelii Spirochetes Using a Transcriptomic Approach. Frontiers in Immunology 11: 612412. [IF=5.085] DOI: 10.3389/fimmu.2020.612412