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1.
Korean J Parasitol ; 60(2): 117-126, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35500893

RESUMO

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-ß and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.


Assuntos
Cistatinas , Fasciola hepatica , Animais , Cistatinas/genética , Cistatinas/metabolismo , Inibidores de Cisteína Proteinase , Fasciola hepatica/genética , Camundongos , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfa
2.
Asian Pac J Cancer Prev ; 23(4): 1177-1183, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35485673

RESUMO

BACKGROUND: Liver fluke caused by Opisthorchis viverrini is a serious health problem in the northeastern region of Thailand. It is associated with endemic cholangiocarcinoma (CCA) in this region. This study was performed to develop a school-based health literacy model for liver fluke prevention and control using participatory action research.   Method: The participants of this study included 3 school administrators, 5 teachers, 45 senior high school students, 2 health officers, and 5 health volunteers. in Phanom Phrai District, Roi-et Province, Thailand. The study employed mixed methods for data collection, including qualitative methods namely policy analysis, interview, and problem-solving as well as quantitative methods namely pre and post-tests and implementation of health literacy. Six months later, researchers evaluated the outcome. The average scores of the participants' health literacy and their practical skills were measured. RESULT: The participants' health literacy and practical skill mean score increased after the intervention (mean difference=20.20, 95%CI 15.37-25.03, p-value <0.001) and (mean difference=21.10, 95%CI 19.10-23.10, p-value <0.001). School activities were concluded regarding public relations for one time a week, exhibitions, learning summary speech contests, and organizing a school food safety club. In addition, school rules were agreed and included: (1) cooked food consumption (2), stopping undercooked cyprinoid fish by the household cooker (3), correcting misunderstanding in each household in the community (4), hygienic defection, and (5) reminding friends to stop consumption of undercooked food. CONCLUSION: The results indicated that school-based model was effective. The stakeholder experiences and learning processes using teamwork will help the development of skills to cooperate and coordinate students choosing the best method for Liver fluke prevention and control. Moreover, they should continue to improve the suitable network for each school to ensure that the models are sustainable.


Assuntos
Neoplasias dos Ductos Biliares , Fasciola hepatica , Letramento em Saúde , Opistorquíase , Animais , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Pesquisa sobre Serviços de Saúde , Humanos , Opistorquíase/epidemiologia
3.
Methods Mol Biol ; 2442: 475-515, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320542

RESUMO

Galectin-11 (LGALS-11) and galectin-14 (LGALS-14) are ruminant specific galectins, first reported in sheep. Although their roles in parasite immunity are still being elucidated, it appears that they influence protection against parasites. In gastrointestinal infections with the nematode Haemonchus contortus, both galectin-11 and galectin-14 appear to be protective. However, in a chronic infection of liver fluke, Fasciola hepatica, these galectins may aid parasite survival. To unravel the structural, functional, and ligand profile of galectin-11 and galectin-14, recombinant production of these proteins is vital. Here we present the recombinant production of soluble galectin-11 and galectin-14 from domestic sheep for in vitro and structural biology studies. These methods include parasite cultivation and infection, galectin staining of host and parasite tissue, surface staining of parasites with recombinant galectins, pull-down assays to identify endogenous galectin binding proteins, and in vitro assays to monitor the effect of galectins on parasite development.


Assuntos
Fasciola hepatica , Fasciolíase , Galectinas , Hemoncose , Haemonchus , Doenças dos Ovinos , Animais , Fasciola hepatica/imunologia , Fasciolíase/imunologia , Fasciolíase/veterinária , Galectinas/genética , Galectinas/fisiologia , Hemoncose/imunologia , Hemoncose/veterinária , Haemonchus/imunologia , Ovinos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/parasitologia , Coloração e Rotulagem
4.
Eur J Pharmacol ; 922: 174899, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35337815

RESUMO

AIM: NMS-P715 is a potent inhibitor of monopolar spindle 1 (MPS1) mitotic checkpoint kinase. Overexpression of MPS1 is associated with short survival times in patients with cholangiocarcinoma (CCA). This study investigated the anti-cancer effects of NMS-P715 in human CCA cell lines. MAIN METHODS: KKU-100 and KKU-213A CCA cell lines were treated with NMS-P715 and cell viability was determined using MTT and colony formation assays. Inhibitory effects of NMS-P715 on cell cycle and apoptosis were evaluated using flow cytometry. Expression of underlying mechanism-related proteins was examined by Western blotting. Mitotic catastrophe was assessed by counting abnormal nuclei. Transwell assays were used to examine cell migration and invasion. KEY FINDINGS: Molecular docking showed that the NMS-P715/MPS1 complex was driven by an induced-fit mechanism. We provide new evidence that NMS-P715 potently inhibited cell proliferation and colony formation in both CCA cell lines. This was accompanied by induction of G2/M arrest and the consequent induction of mitotic catastrophe, a process that occurs during defective mitosis. The recent study showed that NMS-P715 activated caspase-dependent apoptosis and autophagosome formation with an increase of LC3 A/B-II protein expression in CCA cell lines. NMS-P715 also greatly impeded cell migration and invasion in CCA cell lines. The combination of NMS-P715 and gemcitabine or cisplatin showed synergistic effects on CCA cell proliferation. SIGNIFICANCE: This study revealed for the first time that NMS-P715 is a promising candidate for combating CCA owing via multiple actions and may be suitable for further development in a clinical study.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Fasciola hepatica , Animais , Apoptose , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Proliferação de Células , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Pontos de Checagem da Fase G2 do Ciclo Celular , Humanos , Pontos de Checagem da Fase M do Ciclo Celular , Simulação de Acoplamento Molecular , Pirazóis , Quinazolinas
5.
PLoS One ; 17(3): e0265569, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35324959

RESUMO

Fasciolosis is a severe zoonosis responsible for major economic losses in livestock. The enhanced MM3-COPRO test (eMM3-COPRO) and the commercial version BIO K 201 (Bio-X Diagnostics, Rochefort, Belgium) are widely used as immunodiagnostic tools for the specific detection of coproantigens released by Fasciola during the late prepatent and patent stages of infection. However, performance of the eMM3-COPRO has never been evaluated under field conditions. To address this gap, a large number of ovine faecal samples, collected in a region where fasciolosis is endemic (Galicia, NW Spain), were analyzed. Two groups of sheep flocks were selected according to the Fasciola infection status: 'Fasciola-free' and 'Fasciola-infected' flocks. 'Fasciola-free' flocks were seronegative flocks with no history of fasciolosis detected by either coproscopy or necropsy in the last 5 years. Faecal samples from these sheep were used to calculate a cut-off value for infection (OD = 0.021). The cut-off was calculated using a bootstrap resampling method that enables estimation of the sampling distribution of the statistical parameters without making assumptions about the underlying data distribution. 'Fasciola-infected' flocks were characterized by high seroprevalence, a history of fasciolosis and periodical treatment with flukicides. Samples from these flocks were used to estimate the diagnostic accuracy of the eMM3-COPRO relative to coproscopy, which although limited by poor sensitivity is the only reference test available for diagnosing fasciolosis in vivo. To overcome this limitation, all animals classified positive by eMM3-COPRO were treated with triclabendazole and then retested. The eMM3-COPRO displayed higher sensitivity than coproscopy, as it detected coproantigens in all samples with positive coproscopy and in 12% of samples with negative coproscopy. The test also proved highly specific as coproantigens disappeared after the treatment. The eMM3-COPRO was less time consuming than coproscopy, particularly when the procedure involved numerous samples, and showed promise as a tool for monitoring flukicide efficacy.


Assuntos
Fasciola hepatica , Fasciola , Fasciolíase , Doenças dos Ovinos , Animais , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Fasciolíase/diagnóstico , Fasciolíase/epidemiologia , Fasciolíase/veterinária , Fezes , Estudos Soroepidemiológicos , Ovinos , Doenças dos Ovinos/diagnóstico
6.
Acta Trop ; 230: 106394, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35278366

RESUMO

Fasciolosis is a zoonotic disease as 600 million animals have been infected, and 180 million people are at risk of the infection in the world. Snail as the intermediate host of Fasciola is an essential and important factor in the transmission of fasciolosis, while its potential risk for transmission has not been studied. In this study, 3561 snails collected from large-scale regions of China were examined by nest-PCR method. A total of 345 snails were positive for Fasciola spp., with an overall prevalence of 9.7%. Prevalence in central and southern China, characterized by a subtropical monsoon climate, was relatively low (8.0%), while a high infection rate (36.9%) was found on the plateau area (altitude > 500 m). In combination with previous findings, the study showed a highly positive correlation between snails and animal infection in central and eastern China, thus indicating that infected snails could be an indispensable risk factor for fasciolosis transmission. Epidemiological surveillance of snails will help assess the risk of fasciolosis in humans or ruminants, which promotes future prevention of this zoonotic disease.


Assuntos
Fasciola hepatica , Fasciola , Fasciolíase , Animais , Fasciolíase/epidemiologia , Humanos , Ruminantes , Zoonoses/epidemiologia
7.
PLoS Negl Trop Dis ; 16(3): e0010286, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35320269

RESUMO

The tropical liver fluke Fasciola gigantica is a parasitic helminth that has been frequently reported to infect mammals, typically involving water buffaloes. In this study, we characterized the tissue transcriptional landscape of buffaloes following infection by F. gigantica. RNAs were isolated from hepatic lymph nodes (hLNs), peripheral blood lymphocytes (pBLs), and spleen at 3-, 42- and 70-days post-infection (dpi), and all samples were subjected to RNA sequencing analyses. At 3 dpi, 2603, 460, and 162 differentially expressed transcripts (DETs) were detected in hLNs, pBLs, and spleen, respectively. At 42 dpi, 322, 937, and 196 DETs were detected in hLNs, pBLs, and spleen, respectively. At 70 dpi, 376, 334, and 165 DETs were detected in hLNs, pBLs, and spleen, respectively. Functional enrichment analysis identified upregulated immune-related pathways in the infected tissues involved in innate and adaptive immune responses, especially in hLNs at 42 and 70 dpi, and pBLs at 3 and 42 dpi. The upregulated transcripts in spleen were not enriched in any immune-related pathway. Co-expression network analysis further identified transcriptional changes associated with immune response to F. gigantica infection. Receiver operating characteristic (ROC) curve analysis showed that 107 genes in hLNs, 32 genes in pBLs, and 36 genes in spleen correlated with F. gigantica load. These findings provide new insight into molecular mechanisms and signaling pathways associated with F. gigantica infection in buffaloes.


Assuntos
Fasciola hepatica , Fasciola , Fasciolíase , Animais , Búfalos/parasitologia , Fasciola/genética , Fasciola hepatica/genética , Fasciolíase/veterinária , Linfonodos , Linfócitos , Baço , Transcriptoma
8.
Parasite ; 29: 16, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35315767

RESUMO

Fascioliasis is an important zoonotic helminthic disease caused by Fasciola hepatica and poses a serious threat to global public health. To evade the immune response of its host (humans or animals), F. hepatica secretes various antioxidant enzymes such as glutathione transferase (GST) to facilitate its invasion, migration and parasitism in vivo. To investigate the biological functions of a novel omega-class GST (GSTO), the molecular features of GSTO2 of F. hepatica were analyzed by online software, and the biochemical properties in vitro of recombinant GSTO2 (rGSTO2) were dissected. Then, the regulatory roles of rGSTO2 protein in murine macrophages in vitro were further explored. The results revealed that the GSTO2 gene encodes 254 amino acids, which harbor the characteristic N-terminal domain (ßαßαßßα) and C-terminal domain (α-helical) of the cytoplasmic GST superfamily. GSTO2 was mainly expressed in F. hepatica vitelline follicles, intestinal tract, excretory pores and vitelline cells, with thioltransferase and dehydroascorbate reductase activities. Moreover, rGSTO2 protein could be taken up by murine macrophages and significantly inhibit the viability of macrophages. In addition, rGSTO2 protein could significantly promote apoptosis and modulate the expression of cytokines in macrophages. These findings suggested that F. hepatica GSTO2 plays an important role in modulating the physiological functions of macrophages, whereby this protein might be involved in immunomodulatory and anti-inflammatory roles during infection. This study provided new insights into the immune-evasion mechanism of F. hepatica and may contribute to the development of a potential anti-inflammatory agent.


Title: Caractérisation moléculaire d'une nouvelle GSTO2 de Fasciola hepatica et ses rôles dans la modulation des macrophages murins. Abstract: La fasciolase est une importante maladie helminthique zoonotique causée par Fasciola hepatica, qui constitue une menace sérieuse pour la santé publique mondiale. Pour échapper à la réponse immunitaire de son hôte (humain ou animal), F. hepatica sécrète diverses enzymes antioxydantes telles que la glutathion transférase (GST) pour faciliter son invasion, sa migration et son parasitisme in vivo. Pour étudier les fonctions biologiques d'une nouvelle GST de classe oméga (GSTO), les caractéristiques moléculaires de la GSTO2 de F. hepatica ont été analysées par un logiciel en ligne et les propriétés biochimiques in vitro de sa protéine recombinante (rGSTO2) ont été disséquées. Ensuite, les rôles régulateurs de la protéine rGSTO2 sur les macrophages murins in vitro ont été explorés plus avant. Les résultats ont révélé que le gène GSTO2 code pour 254 acides aminés, qui abritent le domaine N-terminal caractéristique (ßαßαßßα) et le domaine C-terminal (α-hélicoïdal) de la superfamille GST cytoplasmique. Chez F. hepatica, GSTO2 était principalement exprimée dans les follicules vitellins, le tractus intestinal, les pores excréteurs et les cellules vitellines, avec des activités de thioltransférase et de déhydroascorbate réductase. De plus, la protéine rGSTO2 a pu être absorbée par les macrophages murins et inhiber de manière significative la viabilité des macrophages. Enfin, la protéine rGSTO2 a pu favoriser de manière significative l'apoptose et moduler l'expression des cytokines dans les macrophages. Ces résultats suggèrent que la GSTO2 de F. hepatica joue un rôle important dans la modulation des fonctions physiologiques des macrophages, cette protéine pouvant être impliquée dans des rôles immunomodulateurs et anti-inflammatoires au cours de l'infection. Cette étude a fourni de nouvelles informations sur le mécanisme d'évasion immunitaire de F. hepatica et pourrait contribuer au développement d'un agent anti-inflammatoire potentiel.


Assuntos
Fasciola hepatica , Fasciolíase , Glutationa Transferase , Macrófagos , Animais , Citocinas , Fasciola hepatica/enzimologia , Fasciola hepatica/genética , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Macrófagos/parasitologia , Camundongos
9.
Vet Parasitol Reg Stud Reports ; 29: 100705, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35256117

RESUMO

A survey of livestock producers (graziers) located in north eastern NSW Australia, collected information on perceptions and management practices for liver fluke control in livestock. The total area farmed by the 161 respondents was 195,600 ha (ranging in size from 4 to 10,522 ha) with cattle and sheep being the dominant livestock enterprises. Overall, 80% of graziers relied exclusively on anthelmintics for liver fluke control and few of these graziers (9%) integrated parasite management (IPM) strategies to reduce disease prevalence. Of those relying on anthelmintic control, triclabendazole (TCBZ) was preferentially chosen by 75% of graziers. Fifty five percent of these graziers used TCBZ in combination with oxfendazole (46%), ivermectin (5%) or abamectin (4%) whilst 45% used TCBZ as a single active ingredient. Thirty eight percent of graziers drenched livestock one or more times per year for liver fluke despite claiming they had no liver fluke or confirmed knowledge of infection. Fifty one percent of graziers based anthelmintic dose on the known weight of the heaviest animal in the herd whilst 43% visually guessed livestock bodyweight to calculate anthelmintic dose. Choice of anthelmintic was predominately based on perceived efficacy (45%) despite very few graziers (2%) having conducted post-treatment fluke egg counts. The majority of graziers (76%) were unsure if they had anthelmintic resistance, 21% claimed they had no resistance whilst 3% of graziers had confirmed resistance. Most graziers (97%) also reported farms were cohabited by kangaroos highlighting additional grazing pressures on-farm. This current survey has revealed that graziers rely on anthelmintics as their primary choice for liver fluke control. Reluctance to adopt IPM strategies and a continued heavy reliance on TCBZ, whilst basing anthelmintic decisions on perception rather than measurement and testing, pose threats for the future control of liver fluke in livestock within this endemic area.


Assuntos
Anti-Helmínticos , Fasciola hepatica , Fasciolíase , Doenças dos Ovinos , Animais , Anti-Helmínticos/uso terapêutico , Austrália , Bovinos , Fasciolíase/tratamento farmacológico , Fasciolíase/epidemiologia , Fasciolíase/prevenção & controle , Fasciolíase/veterinária , Gado , Ovinos , Doenças dos Ovinos/parasitologia , Triclabendazol/uso terapêutico
10.
Vet Parasitol Reg Stud Reports ; 28: 100682, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35115121

RESUMO

The aim of this study was to determine the prevalence and risk of Fasciola hepatica infection in water buffaloes (Bubalus bubalis) during peripartum in southeastern Mexico. An observational study was designed, in which 94 pregnant buffalo cows near calving and naturally exposed to F. hepatica were included. Farm visits were made on days 60, 30, 15 prepartum, at calving, and on days 15 and 30 postpartum. Feces were obtained from all animals to confirm the presence of F. hepatica eggs. A group of 49 animals was randomly treated twice at day 60 prepartum and at calving with nitroxynil and the other group (n = 45) was kept untreated. Buffaloes would be treated once presenting a positive coproparasitological diagnosis up to 30 days postpartum. F. hepatica was detected in 5.3% of the buffaloes (5/94) with a prevalence between 1.7 and 12%. It was observed that treated buffaloes had a lower risk (4.08%) of being positive than untreated buffaloes (6.67%) (P > 0.05). It was also found that untreated animals had 1.6 times more risk of being positive than treated buffaloes. This paper presents the first report of F. hepatica in water buffaloes in Mexico, demonstrating that the two preventive treatments reduced F. hepatica egg shedding during parturition. These findings highlight the need for monitoring for F. hepatica even in unreported/silent potential disease areas.


Assuntos
Doenças dos Bovinos , Fasciola hepatica , Fasciolíase , Animais , Búfalos , Bovinos , Doenças dos Bovinos/epidemiologia , Fasciolíase/epidemiologia , Fasciolíase/veterinária , Fezes , Feminino , México/epidemiologia , Gravidez
11.
Front Cell Infect Microbiol ; 12: 811123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223544

RESUMO

The liver fluke, Fasciola hepatica, is a global burden on the wellbeing and productivity of farmed ruminants, and a zoonotic threat to human health. Despite the clear need for accelerated discovery of new drug and vaccine treatments for this pathogen, we still have a relatively limited understanding of liver fluke biology and host interactions. Noncoding RNAs, including micro (mi)RNAs, are key to transcriptional regulation in all eukaryotes, such that an understanding of miRNA biology can shed light on organismal function at a systems level. Four previous publications have reported up to 89 mature miRNA sequences from F. hepatica, but our data show that this does not represent a full account of this species miRNome. We have expanded on previous studies by sequencing, for the first time, miRNAs from multiple life stages (adult, newly excysted juvenile (NEJ), metacercariae and adult-derived extracellular vesicles (EVs)). These experiments detected an additional 61 high-confidence miRNAs, most of which have not been described in any other species, expanding the F. hepatica miRNome to 150 mature sequences. We used quantitative (q)PCR assays to provide the first developmental profile of miRNA expression across metacercariae, NEJ, adult and adult-derived Evs. The majority of miRNAs were expressed most highly in metacercariae, with at least six distinct expression clusters apparent across life stages. Intracellular miRNAs were functionally analyzed to identify target mRNAs with inversely correlated expression in F. hepatica tissue transcriptomes, highlighting regulatory interactions with key virulence transcripts including cathepsin proteases, and neuromuscular genes that control parasite growth, development and motility. We also linked 28 adult-derived EV miRNAs with downregulation of 397 host genes in F. hepatica-infected transcriptomes from ruminant lymph node, peripheral blood mononuclear cell (PBMC) and liver tissue transcriptomes. These included genes involved in signal transduction, immune and metabolic pathways, adding to the evidence for miRNA-based immunosuppression during fasciolosis. These data expand our understanding of the F. hepatica miRNome, provide the first data on developmental miRNA regulation in this species, and provide a set of testable hypotheses for functional genomics interrogations of liver fluke miRNA biology.


Assuntos
Vesículas Extracelulares , Fasciola hepatica , MicroRNAs , Animais , Fasciola hepatica/genética , Leucócitos Mononucleares , MicroRNAs/genética
12.
Infect Genet Evol ; 99: 105248, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35183754

RESUMO

Parthenogenetic Fasciola is the causative agent of fascioliasis in animals and humans and is widely distributed in Asian countries, such as Japan, South Korea, China, Vietnam, Thailand, the Philippines, Myanmar, Bangladesh, Nepal, and India. Parthenogenetic Fasciola geographically originated from central and eastern China, where it exists between the habitats of Fasciola hepatica and Fasciola gigantica; it likely appeared thousands of years ago following hybridization between F. hepatica and F. gigantica. Parthenogenetic Fasciola consists of diploids and triploids that possess nuclear genome of both F. hepatica and F. gigantica and mitochondrial genome of either F. hepatica or F. gigantica. Maternal parents of parthenogenetic Fasciola are either F. hepatica having Fh-C4 haplotype or F. gigantica having Fg-C2 haplotype in mitochondrial NADH dehydrogenase subunit 1 (ND1) nucleotide sequences. Parthenogenetic Fasciola flukes with the Fh-C4 haplotype have spread from China to South Korea and Japan, whereas the flukes with the Fg-C2 haplotype have not only spread to Korea and Japan but also southward to Vietnam, Thailand, the Philippines, Myanmar, Bangladesh, Nepal, and India. Parthenogenetic Fasciola can be distinguished from F. hepatica and F. gigantica using combinational DNA sequence analysis of nuclear phosphoenolpyruvate carboxykinase (pepck) and DNA polymerase delta (pold) along with mitochondrial ND1 markers. The establishment of parthenogenetic Fasciola is expected as follows: parthenogenetic diploids with the Fh-C4 and Fg-C2 haplotypes first appeared based on single or multiple interspecific hybridization events; subsequently, parthenogenetic triploids emerged via backcross events between the maternal parthenogenetic diploid and either paternal bisexual F. hepatica or F. gigantica. Parthenogenetic Fasciola diploids and triploids then survived for thousands of years by clonal parthenogenetic reproduction, and generated descendants with ND1 haplotypes, which were derived from the Fh-C4 and Fg-C2 due to nucleotide substitution. Thus, the emergence of parthenogenetic Fasciola may be due to extremely uncommon and accidental events. Parthenogenetic Fasciola should be treated as a new asexual hybrid species.


Assuntos
Doenças dos Bovinos , Fasciola hepatica , Fasciola , Fasciolíase , Partenogênese , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Fasciola/genética , Fasciola hepatica/genética , Fasciolíase/epidemiologia , Fasciolíase/veterinária , Humanos , NADH Desidrogenase/genética , Tailândia , Triploidia
13.
Exp Parasitol ; 235: 108231, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35151653

RESUMO

Fasciola hepatica is a trematode worm that causes fascioliasis, a neglected tropical disease in humans and livestock. To gain insight into the host-parasite interactions that facilitate infection, we have investigated the immunomodulatory properties of the parasite's tegumental coat (FhTeg), a major antigen source that is sloughed off and renewed every 2-3 h as the worm migrates through host tissue. Using mouse models of infection, we have previously shown that FhTeg induces a novel phenotype of dendritic cells that induce anergic CD4+ T-cells. We proposed that this induced state of hyporesponsiveness characterised by suppression of cell proliferation and cytokine secretion was one mechanism by which F. hepatica prevented host protective immunity to support the parasite survival. To determine if the same mechanisms are utilised during human infections, we have now examined the interaction of FhTeg with human PBMCs. FhTeg binds to and modulates cytokine production in human PBMCs, in particular targeting the CD4+ population resulting in reduced levels of TNF, IL-2 and IFNγ and increased markers of anergy. Furthermore, the adoptive transfer of FhTeg stimulated PBMCs to a humanised model of acute graft versus host disease (GvHD) attenuated disease progression by increasing survival and reducing pathological scores. These mice also displayed a significant decrease in the total number of human CD4+ cells expressing TNF, IL-2 and IFNγ in the spleen, liver and lung. This study therefore concurs with evidence from ruminant and murine models of infection suggesting that anergic CD4+ T cells are associated with successful Fasciola hepatica infection and highlights an important role for FhTeg in contributing to the overall immunosuppressive effects of this parasite.


Assuntos
Fasciola hepatica , Fasciolíase , Doença Enxerto-Hospedeiro , Animais , Antígenos de Helmintos , Progressão da Doença , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Camundongos , Camundongos Endogâmicos BALB C
14.
Front Immunol ; 13: 794186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35140717

RESUMO

One of the most interesting biological models is that of snail-trematode interactions, many of which ultimately result in the transmission of several important diseases, particularly in the tropics. Herein, we review the scientific advances on a trematode-snail system in which certain populations of Pseudosuccinea columella (a common host species for trematodes) have been demonstrated naturally-resistant to Fasciola hepatica, in association with an effective encapsulation of the parasite by innate immune cells of the host, the hemocytes. Emphasis is made on the molecular and immunological features characterizing each P. columella phenotype in relation to their anti-parasitic competence, their distinctive ecological patterns and the existence of a significant cost of resistance. An integrative overview of the resistance to F. hepatica through comparative immunobiology, genetics and ecology is presented to hypothesize on the possible origins and evolution of this phenomenon and to postulate significant roles for parasite mediated-selection and environmental factors in shaping and maintaining the resistant phenotype in the field. Lastly, clues into future experimental perspectives to deeply characterize the interplay between P. columella and F. hepatica and the immunobiology of the resistance are also included. The advances revised in the present paper are only beginning to unravel mechanisms of anti-parasite innate defense responses and their evolutionary bases, and can facilitate the development of prospective approaches towards practical applications of P. columella resistance.


Assuntos
Doenças dos Animais/parasitologia , Suscetibilidade a Doenças , Fasciola hepatica , Fasciolíase/veterinária , Interações Hospedeiro-Parasita , Caramujos/parasitologia , Animais , Evolução Biológica , Cuba
15.
Parasitol Int ; 88: 102555, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35131471

RESUMO

Fascioliasis is a foodborne zoonotic disease generally caused by the parasitic flukes Fasciola gigantica and Fasciola hepatica in class Trematoda. An "intermediate" Fasciola forms between F. gigantica and F. hepatica has been shown to exist. However, the relationships among F. gigantica, F. hepatica, and "intermediate" Fasciola forms remain unclear. In this study, we found five new polymorphic positions in 18S and 28S rDNAs sequences of "intermediate" Fasciola forms. According to the high-throughput sequencing results, all known 16 polymorphic positions of "intermediate" Fasciola forms show a clear and consistent tendency for F. gigantica or F. hepatica, and the percentages of the most frequently occurring bases were different in specimens. In the three ITS sequence fragments, hybrid-type base combinations of the polymorphic positions were detected, and the percentages of the most frequent base combinations were different in specimens too. In addition, interestingly, the newly detected ITS-802 position was not a traditional polymorphic position in "intermediate" Fasciola forms, and the bases in ITS-802 position are not same as the allele bases of F. gigantica or F. hepatica. Our results will be helpful to investigations into the molecular taxonomy, population genetics, and ecology of F. gigantica, F. hepatica, and "intermediate" Fasciola forms.


Assuntos
Fasciola hepatica , Fasciola , Fasciolíase , Animais , DNA Ribossômico , Fasciola/genética , Fasciola hepatica/genética , Fasciolíase/parasitologia , Sequenciamento de Nucleotídeos em Larga Escala
16.
Prev Vet Med ; 200: 105579, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35066320

RESUMO

We aimed to estimate 1) the marginal effect of liver fluke (Fasciola hepatica) infection on productivity of Scottish beef cattle, and 2) the associated greenhouse gas emissions intensity (GHG EI). Data comprised 240,065 abattoir records from NE Scotland from 2014 to 2017, including the presence or absence of lesions typical of liver fluke in the liver at the time of slaughter, from which we inferred liver fluke infection status. The retrospective analysis of abattoir records to estimate marginal effects of an exposure is complicated by the multi-dimensional, clustered nature of the datasets, which result in confounding of potential causal factors with the exposure. Causal inference methods are required to identify and correct for variation in background exposure. We constructed directed acyclic graphs (DAGs) of observed variables, including the potential confounders, breed, sex, breeder, finisher, season of birth and year of birth. We then applied inverse probability weighting (IPW) to adjust for variation among exposure risk and applied a doubly robust generalized linear model (DRGLM) to the weighted observations to estimate the marginal effect of fluke on the growth rate of animals and total days from birth until slaughter. We compared these estimates with the results of linear mixed effects (LME) models with the same variables, treating breeder and producer as random effects. To estimate GHG EI, we applied IPCC tier-2 type GHG calculations to the marginal effects estimated from IPW with DRGLM. The IPW with DRGLM model estimated that animals with active fluke lesions (adult fluke seen on postmortem inspection) gained 17 (95 % CI 12-22) g/d less saleable beef than animals with no lesions and no visible fluke. Animals with active fluke lesions were 11 (95 % CI 6.5-15) d older at slaughter weight than animals with no lesions. Animals with historic lesions in which there was scarring of the liver but in which no adult fluke were seen showed a wide variation in effect estimates, consistent with some misclassification. The effect estimates from LME models suggested slightly lower effects of fluke on growth rate and days to slaughter but with overlapping 95 % confidence intervals. Calculation of the associated GHG emissions suggest the EI of meat from a herd with no fluke is approximately 1.5 % lower than the same herd with fluke. Sustainably controlling liver fluke would have additional production benefits not included in this estimate and could therefore have a much greater impact on GHG EI in practice than demonstrated here.


Assuntos
Doenças dos Bovinos , Fasciola hepatica , Fasciolíase , Gases de Efeito Estufa , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Fasciolíase/veterinária , Estudos Retrospectivos
17.
Prev Vet Med ; 200: 105569, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35042123

RESUMO

Fasciolosis caused by the trematode Fasciola hepatica is an important parasitosis in both livestock and humans across the globe. Chronic infections in cattle are associated with considerable economic losses. As a prerequisite for an effective control and prevention of fasciolosis in cattle fine-scale predictive models on farm-level are needed. Since disease transmission will only occur where the mollusc intermediate host is present, the objective of our research was to develop a regression model that allows to predict the local presence or absence of Galba truncatula as principal intermediate host for Fasciola hepatica in Switzerland. By implementing generalized linear mixed models (GLMMs) a total amount of 70 variables were analysed for their potential influence on the likelihood πi of finding Galba truncatula at a certain site. Important site-specific features could be considered by selecting suitable modelling procedures. The statistical software R was used to conduct regression analysis, performing the grplasso and the glmmLasso method. The selection of parameters was based on 10-fold cross validation and the Bayesian Information Criterion (BIC). This yielded a total number of 19 potential predictor variables for the grplasso and 13 variables for the glmmLasso model, which also included random effects. Nine variables appeared to be relevant predictors for the occurrence of Galba truncatula in both models. These included reed/humid area, spring water, water bodies within a 100 m radius, and trees/bushes as powerful positive predictors. High soil depth, temperatures frequently exceeding 30 °C in the year preceding the search for snails and temperatures below 0 °C especially in the second year before were identified to exert an adverse effect on the occurrence of Galba truncatula. Temperatures measured near ground level proved to be more powerful predictors than macroclimatic parameters. Precipitation values seemed to be of minor impact in the given setting. Both regression models may be convenient for a fine-scale prediction of the occurrence of Galba truncatula, and thus provide useful approaches for the development of future spatial transmission models, mapping the risk of fasciolosis in Switzerland on farm-level.


Assuntos
Fasciola hepatica , Fasciolíase , Animais , Teorema de Bayes , Bovinos , Fasciolíase/epidemiologia , Fasciolíase/veterinária , Aprendizado de Máquina , Caramujos , Suíça/epidemiologia
18.
Parasitol Res ; 121(4): 1145-1153, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35067744

RESUMO

Understanding drug penetration, distribution, and metabolization is fundamental for understanding drug efficacy. This also accounts for parasites during antiparasitic treatment. Recently, we established matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) in blood flukes and liver flukes. This label-free technique is capable of visualizing the molecular distribution of endogenous and exogenous molecules, such as drug compounds. Here, we conducted atmospheric-pressure scanning microprobe MALDI MSI (AP-SMALDI MSI) of tissue sections of adult Fasciola hepatica that have been treated in vitro with 100 µM of triclabendazole (TCBZ), the drug of choice for treatment of fasciolosis, and its main metabolite triclabendazole sulfoxide (TCBZ-SO). Measurements covered an m/z mass range of 250-1,000 and provided a high spatial resolution using a pixel size of 10 µm. To support the interpretation of drug distribution, we first identified endogenous lipids that mark characteristic tissues such as the gastrodermis, the tegument, and the parenchyma. The obtained results suggested an early tegumental route of TCBZ uptake within 20 min, followed by spreading throughout the parasite after 4 h, and an even distribution in most tissues after 12 h. This coincided with a strong reduction of parasite vitality. TCBZ-SO treatment demonstrated the accumulation of this metabolite in the same tissues as the parent drug compound. These data demonstrate the auspicious potential of MALDI MSI to visualize uptake and distribution patterns of drugs or drug-candidate compounds in parasites, which might contribute to preclinical drug discovery in liver fluke research and beyond.


Assuntos
Anti-Helmínticos , Fasciola hepatica , Fasciolíase , Navegação Espacial , Animais , Anti-Helmínticos/uso terapêutico , Benzimidazóis , Fasciola hepatica/metabolismo , Fasciolíase/tratamento farmacológico , Fasciolíase/parasitologia , Espectrometria de Massas
19.
Parasitol Res ; 121(2): 623-631, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34985596

RESUMO

Protein phosphorylation plays key roles in a variety of essential cellular processes. Fasciola gigantica is a tropical liver fluke causing hepatobiliary disease fascioliasis, leading to human health threats and heavy economic losses. Although the genome and protein kinases of F. gigantica provided new insights to understand the molecular biology and etiology of this parasite, there is scant knowledge of protein phosphorylation events in F. gigantica. In this study, we characterized the global phosphoproteomics of adult F. gigantica by phosphopeptide enrichment-based LC-MS/MS, a high-throughput analysis to maximize the detection of a large repertoire of phosphoproteins and phosphosites. A total of 1030 phosphopeptides with 1244 phosphosites representing 635 F. gigantica phosphoproteins were identified. The phosphoproteins were involved in a wide variety of biological processes including cellular, metabolic, and single-organism processes. Meanwhile, these proteins were found predominantly in cellular components like membranes and organelles with molecular functions of binding (51.3%) and catalytic activity (40.6%). The KEGG annotation inferred that the most enriched pathways of the phosphoproteins included tight junction, spliceosome, and RNA transport (each one contains 15 identified proteins). Combining the reports in other protozoa and helminths, the phosphoproteins identified in this work play roles in metabolic regulation and signal transduction. To our knowledge, this work performed the first global phosphoproteomics analysis of adult F. gigantica, which provides valuable information for development of intervention strategies for fascioliasis.


Assuntos
Fasciola hepatica , Fasciola , Fasciolíase , Animais , Cromatografia Líquida , Humanos , Espectrometria de Massas em Tandem
20.
Parasit Vectors ; 15(1): 33, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35062999

RESUMO

BACKGROUND: Nature conservation with reduced drainage of pastures has been increasingly promoted in agriculture in recent years. However, moisture on pastures is a crucial factor for the development of free-living stages of many parasite species in ruminants. Hence, for the first time, we conducted a field study between 2015 and 2017 at the German North Sea coast to investigate the long-term effect of pasture rewetting (since 2004) on endoparasite infections in sheep and cattle. METHODS: We examined faecal samples of 474 sheep and 646 cattle from five farms in spring, summer and autumn each year for the presence of endoparasite infections. Animals were kept on conventionally drained, undrained and rewetted pastures. The association between pasture rewetting and endoparasite infection probability was analysed in generalized linear mixed models and including further potential confounders. RESULTS: Infection frequencies for gastrointestinal strongyles, Eimeria spp. and Strongyloides papillosus were significantly higher in sheep (62.9%, 31.7% and 16.7%) than in cattle (39.0%, 19.7% and 2.6%). Fasciola hepatica was detected with a frequency of 13.3% in sheep and 9.8% in cattle, while rumen fluke frequency was significantly higher in cattle (12.7%) than in sheep (3.8%). Nematodirus spp., lungworms (protostrongylids, Dictyocaulus viviparus), Moniezia spp., Trichuris spp. and Dicrocoelium dendriticum were identified in less than 7% of samples. Co-infection with more than three endoparasite taxa was present significantly more often in sheep than in cattle. We identified significant positive correlations above 0.2 for excretion intensities between S. papillosus with strongyles, Eimeria spp. and Nematodirus spp. in sheep and between strongyles and Nematodirus spp. in cattle. Pasture rewetting had no long-term effect on endoparasite infections, neither in sheep nor in cattle. Interestingly, F. hepatica infections decreased significantly in sheep and cattle from 2015 (10.9% and 13.9%) to 2017 (1.4% and 2.1%). CONCLUSIONS: Pasture rewetting for nature conservation did not increase endoparasite infection probability in ruminants in the long term. This finding should be confirmed in ongoing studies aimed at further animal welfare parameters. The rapid decrease in F. hepatica infections over 3 years may suggest climatic impact or competition with rumen flukes in addition to potential anthelmintic treatment after feedback of the results to the farmers.


Assuntos
Doenças dos Bovinos , Eimeria , Fasciola hepatica , Doenças dos Ovinos , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Conservação dos Recursos Naturais , Dictyocaulus , Fezes , Ovinos , Doenças dos Ovinos/epidemiologia
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