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).

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.

There is an increasing interest on the effect of global changes on the transmission of infectious diseases. Both environmental and anthropogenic changes are expected to promote outbreaks and spread of pathogens. In particular, tropical infectious diseases are expected to move towards more temperate latitudes. Until 2013, urogenital Schistosomiasis was restricted to tropical and sub-tropical areas. In summer 2013, a schistosomiasis outbreak has emerged in Corsica with more than 100 cases. Corsica is a French Mediterranean island, which is very popular for tourists from throughout Europe due to the natural beauty of the environment. In summer 2015 and 2016, the contamination has resumed and schistosomiasis has been classified in the list of French notifiable infectious disease, making this parasitosis a "not only" tropical disease. Genomic analysis shows that the parasite incriminated is not the pure usual parasite involved in human urogenital schistosomiasis (Schistosoma haematobium), but rather an hybrid between the latter and a parasite infecting animals (S. bovis). The hybrid status of the parasite makes the epidemiological situation much more complex by increasing the risk of (i) higher compatibility/virulence for both invertebrate and vertebrate hosts (i.e. hybrid vigor) (ii) widening the host spectrum and the zoonotic transmission consequences (iii) selecting for drug tolerant parasites (iv) impairing the diagnosis efficiency. HySWARM project is based on an experimental evolution protocol that consists in creating hybrid parasite lines with controlled genetic background. For this purpose, we will first cross the two pure species using reciprocal crosses then we will apply two successive inbreeding backcrosses with either S. bovis or S. haematobium pure species. According to the parasite introgression level from either the human or the animal parasite forms we propose to subsequently analyze (i) the parasite hybrid vigor in the European environmental context (ii) the tolerance of the parasite to the unique treatment used to fight schistosomiasis (praziquantel) (iii) the ability of the parasite to wider its host spectrum (both mollusc and vertebrate) (iv) to analyze the molecular determinants of the host/parasite virulence using a dual approach (RNAseq and DNAseq) (v) to improve diagnosis efficiency by parasitological stool examination (feces and urine), DNA or antigen detection (vi) to reinstate the results obtained from the laboratory to the real ecological situation in the field. In agreement with the One Health concept, our project will bring together experts in the fields of evolutionary biology and ecology, omics data analyses, eco-epidemiology, veterinary science and medicine. Together they will deliver a project working towards the ultimate goal of adequate risk assessment and effective control strategies for disease transmission in a changing world.

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.