Ixodes ricinus, is the most prominent tick vector of disease-causing viral, bacterial, and protozoan agents in Europe. Activities of tick salivary glands, play a pivotal role in tick-borne pathogen transmissions. Neuropeptidergic axons, originating from distinct neuronal cells, innervate several hundreds of saliva producing acini in the salivary glands. Although the superior power of these neurons has been propose their activities are not well understood. We have obtained an unique evidence that two different types of cholinergic receptors are co-expressed in the terminals of these axons likely mediating neuropeptides release for their downstream effect in the glands. Here, we aim to use cutting edge molecular, biochemical, pharmacological and electrophysiological tools to uncover the nature of this unique system. Our study, has the strong potential to identify powerful targets, to disturb tick salivary glands function and subsequently the transfer of tick-borne pathogens.

Giardiasis is a widespread intestinal parasitic disease caused by the protozoan Giardia intestinalis. This digestive parasitosis is considered a neglected disease by the World Health Organization (WHO). Giardiasis is very common, affecting children in particular, and can go unnoticed in some patients. Symptoms include mild to severe or even chronic diarrhea, vomiting, abdominal pain, fatigue and weight loss in case of massive infections. Giardiasis also affects many mammals, including pets such as dogs and cats as well as livestock (ruminants, pigs, etc.). Current treatments are limited to a few anti-infective drugs, but the emergence and spread of resistant strains pose problems for human and animal health. New means of control, such as the use of probiotics, are therefore necessary. Probiotics are "live microorganisms that, when ingested in sufficient quantities, exert positive health effects beyond the traditional nutritional effects". Although they are used in human and veterinary medicine, probiotics remain largely unstudied in the fight against parasitic diseases, even though they represent promising therapeutic alternatives. Several studies have described the ability of certain strains of probiotics to control Giardia proliferation with beneficial effects on the hosts, but their mechanisms of action remain poorly elucidated. Our interdisciplinary consortium of parasitologists, microbiologists and veterinarians has discovered a molecular mechanism based on the action of enzymes produced by certain probiotic strains, bile-salt hydrolases (BSH), which are able to control the growth of Giardia in culture by metabolizing certain non-toxic bile components into their deconjugated derivatives that are toxic to the parasite. In particular, we found that probiotic strains of lactobacilli naturally rich in BSH activities were able to better control the proliferation of Giardia, both in culture, in experimentally infected mice and in puppies naturally infected with Giardia. In these animals, the parasite load and the cyst excretion were reduced. This parasite load could also be reduced by directly using recombinant BSH enzymes (rBSH). We have patented this discovery and wish to continue to explore the use of probiotic lactobacilli BSH as an innovative therapeutic solution for the control of giardiasis in human and veterinary medicine. Although in culture, BSH act against Giardia indirectly via the production of deconjugated bile acids, delivering a signal to the parasite leading to its death, the actual effects and safety of BSH-based therapies in the infected animal are unknown. BileBaG aims to test the effects of these therapies on parasite survival and the host-microbiota-parasite interaction using a mouse model infected with different strains of Giardia. The therapeutic approaches we are considering include improving the anti-Giardia properties of current probiotic candidates by enhancing their BSH activities/stabilities and developing recombinant probiotics. These studies are essential before considering the use of BSH-producing probiotics or recombinant BSH (rBSH), to control this parasite. The BileBaG results could potentially be also be extended to other enteric pathogens that occupy a similar gut environment to Giardia and are potentially controlled in the same manner.

Ticks are the major arthropod vectors transmitting pathogenic agents to humans and domestic animals in Europe, and currently, the incidence of tick-borne disease is rising. The most common European human tick-borne disease is Lyme borreliosis, with an estimated 90 000 new cases every year (compared to 300 000 new cases in the United States annually). This disease is initially clinically diagnosed by the presence of migrating erythema following a tick bite, which is then subsequently confirmed by serological tests. In parallel with classic Lyme borreliosis cases, tick-bitten patients can also present with polymorphic and non-specific clinical symptoms (asthenia, fever, myalgia, etc. …) for which there is no known diagnosis It is extremely difficult to determine the proportion of tick-bitten patients with these symptoms compared to patients which have actually contracted Lyme disease, although it is estimated that 50% of fevers following a tick bite have an unknown infectious origin. The situation is similar for domesticated animals, particularly cattle and dogs which can contract infection from the same tick species as humans. In these animals, only one disease, babeosis, is recognized by veterinarians, however veterinarians and breeders are constantly reporting other tick-related problems and other undiagnosed diseases affecting both French herds and pets. Typical tick habitats are woodlands, prairies, pastures, and gardens. Ticks are extremely sensitive to environmental fluctuations, which are often brought about by human socio-economic changes, thus tick-borne diseases are excellent candidates for emergence. Consequently, it is incontestable that tick-borne diseases pose a significant threat to our society. In addition to improving diagnostic techniques, one of the major hurdles relates to improving public and health professional knowledge about tick disease risk. The battle against tick-borne diseases is based on relatively simple prevention measures, and their effectiveness is immeasurably improved when citizens are more informed and involved. Therefore, we have designed a multidisciplinary project, bringing together veterinarians, doctors, scientists, and consultant sociologists to create a global “One Health” approach to tick-borne diseases. Specific scientific project objectives are to (1) detect, identify, and isolate new microorganisms—both unknown or unexpected—from patients or animals suffering from unexplainable symptoms following tick bites; (2) to demonstrate tick competence in their ability to transmit these agents; and (3) to generate concrete recommendations to improve tick-borne disease management. Due to our multi-disciplinary consortium of experts, we are sure to achieve our goals of generating novel insights into tick-borne disease. These results will be invaluable in the development of novel and improved diagnostic tests, and for the generation and dissemination of up-to-date information to the public. This study will also encompass and promote improved training for veterinary and medical students. We will also generate detailed recommendations for public health authorities to improve overall management of tick-borne diseases.

Although eradication has traditionally been the goal for many infectious diseases, it is not achievable for vector-bone diseases for which multiple epidemiological compartments (urban and sylvatic vector species, domestic and wild hosts, human populations) co-exist and interact in a changing environment. Additionally, although control or preventive measures are available, this may not ultimately impact the success of a programme and lead to the reduction of disease burden. Consideration of socio-economic and cultural factors affecting the livelihood and well-being of farmers and animal breeders can be important incentives for participation or non-compliance. Biological understanding of disease epidemiology is therefore as important as socio-economic considerations of farmers, limitations of stakeholders and communities’ engagement, assessment of attitudes and expectations of the end-users, evaluation of technical tools (diagnostic tests, vaccines, trained staff) and surveillance and control measures. The assessment of these factors should guide the strategic planning and surveillance and control of vector-borne disease programme implementation. Therefore, we present the MAKEDA project (Multi-Actor Knowledge on surveillance and control of Emerging vector-borne animal Diseases in Europe and Africa), regrouping key researchers with expertise on animal and zoonotic vector diseases from leading institutes in Africa and Europe. The MAKEDA project aims at establishing an integrated One-Health approach to characterize emergence and outbreak drivers of vector-borne diseases affecting livestock along an Africa-Europe transect, raising awareness among stakeholders and farmer communities of risks and good practices for surveillance and control, preparing and anticipating current and emerging threats. The originality of the MAKEDA project will be achieved by merging unconventional approaches for surveillance and control of vector-borne diseases (sociological methods, participatory modelling and epidemiology) with classical epidemiological, entomological and microbiological studies to optimize actions in challenging environments. It also owes its originality in contributing towards controlling and monitoring animal diseases by deploying great efforts to integrate numerous inter-sectorial actors into the One Health paradigm and considering of high importance continuous assessment of impact pathway with partners and end-users. To this purpose, the MAKEDA project will link research, national and international animal and public health organizations, and farmer organizations in Europe and Africa to develop. The broad inclusion of experts from animal diseases epidemiology and surveillance, risk modelling and analysis, vaccine development and control strategies, health economy, applied social sciences to livestock disease management and the upstream inclusion from the planning of the project and experiments to implementation and dissemination of the results will ensure involvement of various animal health actors and beneficiaries of the project.

Trichinella spp. are zoonotic parasites considered to be re-emerging and the causative agent of trichinellosis, a disease contracted by eating raw or undercooked infected meat. The newborn larvae of the parasite invade the skeletal muscle cell and divert its transcriptional mechanisms to transform it into a nurse cell. This new structure will serve the larvae’s purpose, i.e. provide shelter and nutrients to grow into an infective muscle larvae. Some Trichinella species also induce the formation of a collagen capsule around the nurse cell, like Trichinella spiralis and some remain unencapsulated (e.g. Trichinella pseudospiralis). This particular host-parasite interaction is well described : it shares features with muscle repair which is a complex interplay between muscle cells and immune cells. Nevertheless, the exact molecular mechanisms remain to be investigated. The goal of the TrichinEVs is to focus on a potential communication vector for the muscle infection process : extracellular vesicles (EVs). Our main questions will concern the content (proteins and microRNAs) of parasite and muscle cells EVs at different stages of the infection and with two Trichinella species (T. spiralis versus T. pseudospiralis) (WP1), the effect of the parasite EVs on muscle and immune cells activation (WP2) and the effect of a previously described parasite protein, NBL1, on muscle cells EV production (WP3).