Trematodes of the order Diplostomida are well known as serious pathogens of man, and both farm and wild animals; members of the genus Schistosoma (Schistosomatidae) are responsible for human schistosomosis (schistosomiasis) affecting more than 200 million people in tropical and subtropical countries, and infections of mammals and birds by animal schistosomes are of great veterinary importance. The order Diplostomida is also rich in species parasitizing other major taxa of vertebrates. The "Aporocotylidae" sensu lato are pathogenic in fish, "Spirorchiidae" sensu lato in reptiles. All these flukes have two-host life cycles, with asexually reproducing larvae usually in mollusks and occasionally in annelids, and adults usually live in the blood vessels of their vertebrate hosts. Pathology is frequently associated with inflammatory reactions to eggs trapped in various tissues/organs. On the other hand, the representatives of Diplostomidae and Strigeidae have three- or four-host life cycles in which vertebrates often serve not only as definitive but also as intermediate or paratenic hosts. Pathology is usually associated with migration of metacercariae and mesocercariae within the host tissues. The impact of these trematode infections on both farm and wild animals may be significant.
Skin uses interdependent cellular networks for barrier integrity and host immunity, but most underlying mechanisms remain obscure. Herein, we demonstrate that the human parasitic helminth Schistosoma mansoni inhibited pruritus evoked by itch-sensing afferents bearing the Mas-related G-protein-coupled receptor A3 (MrgprA3) in mice. MrgprA3 neurons controlled interleukin (IL)-17+ γδ T cell expansion, epidermal hyperplasia and host resistance against S. mansoni through shaping cytokine expression in cutaneous antigen-presenting cells. MrgprA3 neuron activation downregulated IL-33 but induced IL-1β and tumor necrosis factor in macrophages and type 2 conventional dendritic cells partially through the neuropeptide calcitonin gene-related peptide. Macrophages exposed to MrgprA3-derived secretions or bearing cell-intrinsic IL-33 deletion showed increased chromatin accessibility at multiple inflammatory cytokine loci, promoting IL-17/IL-23-dependent changes to the epidermis and anti-helminth resistance. This study reveals a previously unrecognized intercellular communication mechanism wherein itch-inducing MrgprA3 neurons initiate host immunity against skin-invasive parasites by directing cytokine expression patterns in myeloid antigen-presenting cell subsets.
- MeSH
- dendritické buňky imunologie MeSH
- interleukin 33 * metabolismus imunologie MeSH
- kůže imunologie parazitologie MeSH
- lidé MeSH
- makrofágy imunologie metabolismus MeSH
- myeloidní buňky imunologie metabolismus MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- neurony imunologie metabolismus MeSH
- pruritus imunologie MeSH
- receptory spřažené s G-proteiny * metabolismus imunologie genetika MeSH
- Schistosoma mansoni * imunologie MeSH
- schistosomiasis mansoni * imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open-label observational study to establish a controlled human infection model (CHIM) of sand fly-transmitted cutaneous leishmaniasis (CL) caused by Leishmania major. Between 24 January and 12 August 2022, we exposed 14 participants to L. major-infected Phlebotomus duboscqi. The primary objective was to demonstrate effectiveness of lesion development (take rate) and safety (absence of CL lesion at 12 months). Secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. Lesion development was terminated by therapeutic biopsy (between days 14 and 42 after bite) in ten participants with clinically compatible lesions, one of which was not confirmed by parasite detection. We estimated an overall take rate for CL development of 64% (9/14). Two of ten participants had one and one of ten participants had two lesion recurrences 4-8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but as expected, scarring due to a combination of CL and the biopsy procedure was evident. All participants were lesion free at >12-month follow-up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This CHIM offers opportunities for vaccine candidate selection based on human efficacy data and for a greater understanding of immune-mediated pathology. ClinicalTrials.gov identifier: NCT04512742 .
- MeSH
- dospělí MeSH
- Leishmania major * imunologie MeSH
- leishmanióza kožní * imunologie parazitologie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- parazitární zátěž MeSH
- Phlebotomus parazitologie imunologie MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Equids may be infected by zoonotic Leishmania spp., including Leishmania infantum, in regions where canine leishmaniasis (CanL) is endemic, and Leishmania martiniquensis, which has been reported in horses from Central Europe. This study was designed to evaluate the occurrence of both Leishmania spp. among equids living in CanL endemic areas of Italy, as well as to identify dipteran vectors from the same habitats. From March to October 2023, blood, serum and tissue samples from skin lesions were collected from equids (n = 98; n = 56 donkeys and n = 42 horses) living in Italy, as well as sand flies and biting midges. Blood samples (n = 98) and skin lesions (n = 56) were tested for Leishmania spp. by conventional and real time PCRs and sera were tested by immunofluorescence antibody tests (IFAT) for both L. infantum and L. martiniquensis. Insects were morphologically identified, and female specimens (n = 268 sand flies, n = 7 biting midges) analyzed for Leishmania DNA, as well as engorged sand flies (n = 16) for blood-meal detection. Two animals with skin lesions (i.e., one donkey and one horse) scored positive for Leishmania spp. DNA, and 19 animals (i.e., 19.4%; n = 13 donkeys and n = 6 horses) were seropositive for L. infantum, with five of them also for L. martiniquensis. Most seropositive animals had no dermatological lesions (i.e., 68.4%) while both animals molecularly positive for Leishmania spp. scored seronegative. Of the 356 sand flies collected, 12 females (i.e., n = 8 Sergentomyia minuta; n = 3 Phlebotomus perniciosus, n = 1 Phlebotomus perfiliewi) were positive for Leishmania spp. DNA, and one out of seven biting midges collected was DNA-positive for L. infantum. Moreover, engorged sand flies scored positive for human and equine DNA. Data suggest that equids living in CanL endemic areas are exposed to Leishmania spp., but their role in the circulation of the parasite needs further investigations.
- MeSH
- Ceratopogonidae parazitologie MeSH
- endemické nemoci veterinární MeSH
- Equidae * parazitologie MeSH
- hmyz - vektory * parazitologie MeSH
- koně parazitologie MeSH
- Leishmania infantum izolace a purifikace genetika MeSH
- Leishmania * izolace a purifikace genetika klasifikace MeSH
- leishmanióza * veterinární epidemiologie parazitologie přenos MeSH
- nemoci koní parazitologie epidemiologie MeSH
- nemoci psů * parazitologie epidemiologie přenos MeSH
- psi MeSH
- Psychodidae parazitologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- psi MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Itálie MeSH
BACKGROUND: In Europe, avian schistosomes of the genus Trichobilharzia are the most common etiological agents involved in human cercarial dermatitis (swimmer's itch). Manifested by a skin rash, the condition is caused by an allergic reaction to cercariae of nonhuman schistosomes. Humans are an accidental host in this parasite's life cycle, while water snails are the intermediate, and waterfowl are the final hosts. The study aimed to conduct a molecular and phylogenetic analysis of Trichobilharzia species occurring in recreational waters in North-Eastern Poland. METHODOLOGY: The study area covered three water bodies (Lake Skanda, Lake Ukiel, and Lake Tyrsko) over the summer of 2021. In total, 747 pulmonate freshwater snails (Radix spp., Lymnaea stagnalis) were collected. Each snail was subjected to 1-2 h of light stimulation to induce cercarial expulsion. The phylogenetic analyses of furcocercariae were based on the partial sequence of the ITS region (ITS1, 5.8S rDNA, ITS2 and 28SrDNA). For Radix spp. phylogenetic analyses were based on the ITS-2 region. RESULTS: The prevalence of the Trichobilharzia species infection in snails was 0.5%. Two out of 478 (0.4%) L. stagnaliswere found to be infected with Trichobilharzia szidati. Moreover, two out of 269 (0.7%) snails of the genus Radix were positive for schistosome cercariae. Both snails were identified as Radix auricularia. One of them was infected with Trichobilharzia franki and the other with Trichobilharzia sp. CONCLUSIONS: Molecular identification of avian schistosome species, both at the intermediate and definitive hosts level, constitutes an important source of information on a potential threat and prognosis of local swimmer's itch occurrence, and helps to determine species diversity in a particular area.
- MeSH
- DNA helmintů genetika MeSH
- fylogeneze * MeSH
- hlemýždi parazitologie MeSH
- infekce červy třídy Trematoda parazitologie veterinární epidemiologie MeSH
- jezera parazitologie MeSH
- lidé MeSH
- Schistosomatidae * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Polsko MeSH
Leishmania, the dixenous trypanosomatid parasites, are the causative agents of leishmaniasis currently divided into four subgenera: Leishmania, Viannia, Sauroleishmania, and the recently described Mundinia, consisting of six species distributed sporadically all over the world infecting humans and/or animals. These parasites infect various mammalian species and also cause serious human diseases, but their reservoirs are unknown. Thus, adequate laboratory models are needed to enable proper research of Mundinia parasites. In this complex study, we compared experimental infections of five Mundinia species (L. enriettii, L. macropodum, L. chancei, L. orientalis, and four strains of L. martiniquensis) in three rodent species: BALB/c mouse, Chinese hamster (Cricetulus griseus) and steppe lemming (Lagurus lagurus). Culture-derived parasites were inoculated intradermally into the ear pinnae and progress of infection was monitored for 20 weeks, when the tissues and organs of animals were screened for the presence and quantity of Leishmania. Xenodiagnoses with Phlebotomus duboscqi were performed at weeks 5, 10, 15 and 20 post-infection to test the infectiousness of the animals throughout the experiment. BALB/c mice showed no signs of infection and were not infectious to sand flies, while Chinese hamsters and steppe lemmings proved susceptible to all five species of Mundinia tested, showing a wide spectrum of disease signs ranging from asymptomatic to visceral. Mundinia induced significantly higher infection rates in steppe lemmings compared to Chinese hamsters, and consequently steppe lemmings were more infectious to sand flies: In all groups tested, they were infectious from the 5th to the 20th week post infection. In conclusion, we identified two rodent species, Chinese hamster (Cricetulus griseus) and steppe lemming (Lagurus lagurus), as candidates for laboratory models for Mundinia allowing detailed studies of these enigmatic parasites. Furthermore, the long-term survival of all Mundinia species in steppe lemmings and their infectiousness to vectors support the hypothesis that some rodents have the potential to serve as reservoir hosts for Mundinia.
- MeSH
- Arvicolinae * parazitologie MeSH
- Cricetulus MeSH
- křečci praví MeSH
- Leishmania * klasifikace MeSH
- leishmanióza * parazitologie MeSH
- modely nemocí na zvířatech * MeSH
- myši inbrední BALB C * MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Sand fly transmitted Leishmania species are responsible for severe, wide ranging, visceral and cutaneous leishmaniases. Genetic exchange can occur among natural Leishmania populations and hybrids can now be produced experimentally, with limitations. Feeding Phlebotomus orientalis or Phlebotomus argentipes on two strains of Leishmania donovani yielded hybrid progeny, selected using double drug resistance and fluorescence markers. Fluorescence activated cell sorting of cultured clones derived from these hybrids indicated diploid progeny. Multilocus sequence typing of the clones showed hybridisation and nuclear heterozygosity, although with inheritance of single haplotypes in a kinetoplastid target. Comparative genomics showed diversity of clonal progeny between single chromosomes, and extraordinary heterozygosity across all 36 chromosomes. Diversity between progeny was seen for the HASPB antigen, which has been noted previously as having implications for design of a therapeutic vaccine. Genomic diversity seen among Leishmania strains and hybrid progeny is of great importance in understanding the epidemiology and control of leishmaniasis. As an outcome of this study we strongly recommend that wider biological archives of different Leishmania species from endemic regions should be established and made available for comparative genomics. However, in parallel, performance of genetic crosses and genomic comparisons should give fundamental insight into the specificity, diversity and limitations of candidate diagnostics, vaccines and drugs, for targeted control of leishmaniasis.
- MeSH
- genomika MeSH
- křížení genetické MeSH
- Leishmania donovani * genetika MeSH
- leishmanióza kožní * MeSH
- leishmanióza viscerální * diagnóza prevence a kontrola epidemiologie MeSH
- Phlebotomus * genetika MeSH
- Psychodidae * genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Phlebotomine sand flies (Diptera: Phlebotominae) are the principal vectors of Leishmania spp. (Kinetoplastida: Trypanosomatidae). In Central Europe, Phlebotomus mascittii is the predominant species, but largely understudied. To better understand factors driving its current distribution, we infer patterns of genetic diversity by testing for signals of population expansion based on two mitochondrial genes and model current and past climate and habitat suitability for seven post-glacial maximum periods, taking 19 climatic variables into account. Consequently, we elucidate their connections by environmental-geographical network analysis. Most analyzed populations share a main haplotype tracing back to a single glacial maximum refuge area on the Mediterranean coasts of South France, which is supported by network analysis. The rapid range expansion of Ph. mascittii likely started in the early mid-Holocene epoch until today and its spread possibly followed two routes. The first one was through northern France to Germany and then Belgium, and the second across the Ligurian coast through present-day Slovenia to Austria, toward the northern Balkans. Here we present a combined approach to reveal glacial refugia and post-glacial spread of Ph. mascittii and observed discrepancies between the modelled and the current known distribution might reveal yet overlooked populations and potential further spread.
- MeSH
- hmyz - vektory genetika MeSH
- Leishmania * MeSH
- Phlebotomus * genetika MeSH
- Psychodidae * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
With the current expansion of vector-based research and an increasing number of facilities rearing arthropod vectors and infecting them with pathogens, common measures for containment of arthropods as well as manipulation of pathogens are becoming essential for the design and running of such research facilities to ensure safe work and reproducibility, without compromising experimental feasibility. These guidelines and comments were written by experts of the Infravec2 consortium, a Horizon 2020-funded consortium integrating the most sophisticated European infrastructures for research on arthropod vectors of human and animal diseases. They reflect current good practice across European laboratories with experience of safely handling different mosquito species and the pathogens they transmit. As such, they provide experience-based advice to assess and manage the risks to work safely with mosquitoes and the pathogens they transmit. This document can also form the basis for research with other arthropods, for example, midges, ticks or sandflies, with some modification to reflect specific requirements.
- MeSH
- členovci - vektory MeSH
- členovci * MeSH
- Culicidae * MeSH
- komáří přenašeči MeSH
- lidé MeSH
- reprodukovatelnost výsledků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
