Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases.

Summary Borrelia burgdorferi sensu lato (s.l.) complex is a diverse group of worldwide distributed bacteria that includes 18 named spirochete species and a still not named group proposed as genomospecies 2 (Postic et al., 2007). Descriptions of new species and variants continue to be recognized, so the current number of described species is probably not final. Most of known spirochete species are considered to have a limited distribution. Eleven species from the B. burgdorferi s.l. complex were identified in and strictly associated with Eurasia (B. afzelii, B. bavariensis, B. garinii, B. japonica, B. lusitaniae, B. sinica, B. spielmanii, B. tanukii, B. turdi, B. valaisiana, and B. yangtze), while another 5 (B. americana, B. andersonii, B. californiensis, B. carolinensis, and B. kurtenbachii) were previously believed to be restricted to the USA only (Rudenko et al., 2009b, 2009c; Margos et al., 2010). B. burgdorferi sensu stricto (s.s.), B. bissettii, and B. carolinensis share the distinction of being present in both the Old and the New World. Out of the 18 genospecies, 3 commonly and 4 occasionally infect humans, causing Lyme borreliosis (LB) – a multisystem disease that is often referred to as the ‘great imitator’ due to diversity of its clinical manifestations. Among the genospecies that commonly infect people, i.e. B. burgdorferi s.s., B. afzelii, and B. garinii, only B. burgdorferi s.s. causes LB both in the USA and in Europe, with a wide spectrum of clinical conditions ranging from minor cutaneous erythema migrans (EM) to severe arthritis or neurological manifestations. The epidemiological data from many European countries and the USA show a dramatic increase of the diagnosed cases of LB due to the development of new progressive diagnostic methods during the last decades (Hubálek, 2009). Recently, the definition of the disease has also changed. What was not considered Lyme borreliosis before might be now.

Arboviruses are transmitted by distantly related arthropod vectors such as mosquitoes (class Insecta) and ticks (class Arachnida). RNA interference (RNAi) is the major antiviral mechanism in arthropods against arboviruses. Unlike in mosquitoes, tick antiviral RNAi is not understood, although this information is important to compare arbovirus/host interactions in different classes of arbovirus vectos. Using an Ixodes scapularis-derived cell line, key Argonaute proteins involved in RNAi and the response against tick-borne Langat virus (Flaviviridae) replication were identified and phylogenetic relationships characterized. Analysis of small RNAs in infected cells showed the production of virus-derived small interfering RNAs (viRNAs), which are key molecules of the antiviral RNAi response. Importantly, viRNAs were longer (22 nucleotides) than those from other arbovirus vectors and mapped at highest frequency to the termini of the viral genome, as opposed to mosquito-borne flaviviruses. Moreover, tick-borne flaviviruses expressed subgenomic flavivirus RNAs that interfere with tick RNAi. Our results characterize the antiviral RNAi response in tick cells including phylogenetic analysis of genes encoding antiviral proteins, and viral interference with this pathway. This shows important differences in antiviral RNAi between the two major classes of arbovirus vectors, and our data broadens our understanding of arthropod antiviral RNAi.