Relapsing fever still remains a neglected disease and little is known on its reservoir, tick vector and physiopathology in the vertebrate host. The disease occurs in temperate as well as tropical countries. Relapsing fever borreliae are spirochaetes, members of the Borreliaceae family which also contain Lyme disease spirochaetes. They are mainly transmitted by Ornithodoros soft ticks, but some species are vectored by ixodid ticks. Traditionally a Borrelia species is associated with a specific vector in a particular geographical area. However, new species are regularly described, and taxonomical uncertainties deserve further investigations to better understand Borrelia vector/host adaptation. The medical importance of Borrelia miyamotoi, transmitted by Ixodes spp., has recently spawned new interest in this bacterial group. In this review, recent data on tick-host-pathogen interactions for tick-borne relapsing fevers is presented, with special focus on B. miyamotoi.

The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector competence, taking Stomoxys calcitrans as a model. S. calcitrans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so epithelial immune mechanisms, and in particular antimicrobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calcitrans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and secreted exclusively in the anterior midgut of S. calcitrans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhodesiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes causing African sleeping sickness and nagana.

Lyme borreliosis is an arthropod-borne disease transmitted by the Ixodes tick. This spirochetal infection is first characterized by a local cutaneous inflammation, the erythema migrans. The skin constitutes a key interface in the development of the disease. During Borrelia inoculation, tick saliva affects the innate and adaptive immunity of the vertebrate host skin. Some key mediators of innate immunity such as antimicrobial peptides (cathelicidin and defensin families) have been identified as important initiators of skin inflammation. We analyzed the role of tick saliva on integumental innate immunity using different protocols of Borrelia infection, via syringe or direct tick transmission. When syringe inoculation was used, Borrelia triggered skin inflammation with induction of CRAMP, the mouse cathelicidin, and tumor necrosis factor-alpha. However, when Borrelia was transmitted directly via the tick, we observed a significant repression of inflammatory genes, suggesting a critical role of tick saliva in skin innate immunity. For all the protocols tested, a peak of intense Borrelia multiplication occurred in the skin between days 5 and 15, before bacterial dissemination to target organs. We conclude that Borrelia pathogens specifically use the tick saliva to facilitate their transmission to the host and that the skin constitutes an essential interface in the development of Lyme disease.

Ticks are vectors of infectious diseases of major importance in human and veterinary medicine. For epidemiological studies, accurate identification of ticks is crucial to define their potential role as vectors and to develop control and prevention strategies. Although morphological and molecular methods are widely used to identify ticks, an innovative approach using MALDI-TOF MS technology recently emerged as an alternative tool. Previous works showed that MALDI-TOF MS was highly effective in identifying ticks, but these works mainly tested tick specimens of different genera. To confirm the accuracy of this new tool for tick identification, nine closely related tick species belonging to the Ixodes genus were analysed, specimens of the Dermacentor reticulatus species were also included in the analysis as an outer group. Three of the species used for the present study belonged to the I. ricinus species complex, which are known to transmit Borrelia burgdorferi sensu lato, the causative agent of Lyme borreliosis. A total of 246 tick specimens were submitted to MALDI-TOF MS analysis, and two body parts (half-idiosoma and four legs) were individually investigated. For each body part, intraspecies reproducibility and interspecies specificity of the MS profiles were determined. The profile analysis revealed that the main determinant for spectra clustering was the tick species for both legs and half-idiosoma. For each body part, a reference database of spectra was set up including 2 to 5 specimens per species randomly selected, and genotyped using 16s rDNA and COI genes to confirm their morphological identification. Both created spectral databases were individually blind tested with their respective body part using the remaining specimens, which were correctly identified in 98.5% of the cases. MALDI-TOF MS is a reliable tool for tick identification, including specimens belonging to closely related species and hardly distinguishable using morphology. The 4-legs as well as the half-idiosoma of ticks can now be applied for specimen identification using two different databases. The combined use of these two body parts improves the rate of tick identification and their confidence level.