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1.
PLoS Pathog ; 16(8): e1008131, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866196

RESUMO

Invasion of hepatocytes by Plasmodium sporozoites initiates the pre-erythrocytic step of a malaria infection. Subsequent development of the parasite within hepatocytes and exit from them is essential for starting the disease-causing erythrocytic cycle. Identification of signaling pathways that operate in pre-erythrocytic stages provides insight into a critical step of infection and potential targets for chemoprotection from malaria. We demonstrate that P. berghei homologs of Calcium Dependent Protein Kinase 1 (CDPK1), CDPK4 and CDPK5 play overlapping but distinct roles in sporozoite invasion and parasite egress from hepatocytes. All three kinases are expressed in sporozoites. All three are required for optimal motility of sporozoites and consequently their invasion of hepatocytes. Increased cGMP can compensate for the functional loss of CDPK1 and CDPK5 during sporozoite invasion but cannot overcome loss of CDPK4. CDPK1 and CDPK5 expression is downregulated after sporozoite invasion. CDPK5 reappears in a subset of late stage liver stages and is present in all merosomes. Chemical inhibition of CDPK4 and depletion of CDPK5 in liver stages implicate these kinases in the formation and/or release of merosomes from mature liver stages. Furthermore, depletion of CDPK5 in merosomes significantly delays initiation of the erythrocytic cycle without affecting infectivity of hepatic merozoites. These data suggest that CDPK5 may be required for the rupture of merosomes. Our work provides evidence that sporozoite invasion requires CDPK1 and CDPK5, and suggests that CDPK5 participates in the release of hepatic merozoites.


Assuntos
Regulação para Baixo , Regulação Enzimológica da Expressão Gênica , Malária/epidemiologia , Merozoítos/enzimologia , Plasmodium berghei/enzimologia , Proteínas Quinases/biossíntese , Proteínas de Protozoários/biossíntese , Esporozoítos/enzimologia , Animais , Eritrócitos/enzimologia , Eritrócitos/parasitologia , Feminino , Células Hep G2 , Humanos , Fígado/enzimologia , Fígado/parasitologia , Malária/patologia , Camundongos
2.
PLoS Pathog ; 16(9): e1008891, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32956401

RESUMO

The transitions between developmental stages are critical points in the Plasmodium life cycle. The development of Plasmodium in the livers of their mammalian hosts bridges malaria transmission and the onset of clinical symptoms elicited by red blood cell infection. The egress of Plasmodium parasites from the liver must be a carefully orchestrated process to ensure a successful switch to the blood stage of infection. Cysteine protease activity is known to be required for liver-stage Plasmodium egress, but the crucial cysteine protease(s) remained unidentified. Here, we characterize a member of the papain-like cysteine protease family, Plasmodium berghei serine repeat antigen 4 (PbSERA4), that is required for efficient initiation of blood-stage infection. Through the generation PbSERA4-specific antisera and the creation of transgenic parasites expressing fluorescently tagged protein, we show that PbSERA4 is expressed and proteolytically processed in the liver and blood stages of infection. Targeted disruption of PbSERA4 results in viable and virulent blood-stage parasites. However, upon transmission from mosquitoes to mice, Pbsera4(-) parasites displayed a reduced capacity to initiate a new round of asexual blood-stage replication. Our results from cultured cells indicate that this defect results from an inability of the PbSERA4-deficient parasites to egress efficiently from infected cells at the culmination of liver-stage development. Protection against infection with wildtype P. berghei could be generated in animals in which Pbsera4(-) parasites failed to establish infection. Our findings confirm that liver-stage merozoite release is an active process and demonstrate that this parasite-encoded cysteine protease contributes to parasite escape from the liver.


Assuntos
Cisteína Proteases/metabolismo , Fígado/parasitologia , Malária/enzimologia , Plasmodium berghei/enzimologia , Proteínas de Protozoários/metabolismo , Animais , Cisteína Proteases/genética , Fígado/metabolismo , Malária/genética , Camundongos , Plasmodium berghei/genética , Proteínas de Protozoários/genética , Ratos , Ratos Sprague-Dawley
3.
PLoS Negl Trop Dis ; 14(8): e0008635, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32853206

RESUMO

BACKGROUND: In view of the potential immunosuppressive and regenerative properties of mesenchymal stem cells (MSC), we investigated whether transplantation of adipose tissue-derived stem cells (ASC) could be used to control the granulomatous reaction in the liver of mice infected with Schistosoma mansoni after Praziquantel (PZQ) treatment. METHODOLOGY/PRINICPAL FINDINGS: C57BL/6 mice infected with S. mansoni were treated with PZQ and transplanted intravenously with ASC from uninfected mice. Liver morpho-physiological and immunological analyses were performed. The combined PZQ/ASC therapy significantly reduced the volume of hepatic granulomas, as well as liver damage as measured by ALT levels. We also observed that ASC accelerated the progression of the granulomatous inflammation to the advanced/curative phase. The faster healing interfered with the expression of CD28 and CTLA-4 molecules in CD4+ T lymphocytes, and the levels of IL-10 and IL-17 cytokines, mainly in the livers of PZQ/ASC-treated mice. CONCLUSIONS: Our results show that ASC therapy after PZQ treatment results in smaller granulomas with little tissue damage, suggesting the potential of ASC for the development of novel therapeutic approaches to minimize hepatic lesions as well as a granulomatous reaction following S. mansoni infection. Further studies using the chronic model of schistosomiasis are required to corroborate the therapeutic use of ASC for schistosomiasis.


Assuntos
Tecido Adiposo/fisiologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Hepatopatias/terapia , Fígado/parasitologia , Praziquantel/uso terapêutico , Esquistossomose/tratamento farmacológico , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Granuloma , Fígado/metabolismo , Fígado/patologia , Hepatopatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Schistosoma mansoni , Esquistossomose/patologia , Esquistossomose mansoni
4.
Parasitol Res ; 119(9): 3041-3051, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32779021

RESUMO

Our objective was to investigate clinical progression, presence of parasites and DNAs, parasite loads, and histological alterations in BALB/c mice and Syrian golden hamsters after intraperitoneal inoculation with Leishmania (Mundinia) martiniquensis promastigotes with a goal to choosing an appropriate animal model for visceral leishmaniasis. Infections were monitored for 16 weeks. Infected BALB/c mice were asymptomatic during the infection course. Parasite DNAs were detected in the liver at week 8 of infection, followed by clearance in most animals at week 16; whereas in the spleen, parasite DNAs were detected until week 16. These results are correlated to those obtained measuring parasite loads in both organs. No parasite DNA and no alteration in the bone marrow were observed indicating that no dissemination occurred. These results suggest the control of visceralization of L. martiniquensis by BALB/c mice. In hamsters, weight loss, cachexia, and fatigue were observed after week 11. Leishmania martiniquensis parasites were observed in tissue smears of the liver, spleen, and bone marrow by week 16. Parasite loads correlated with those from the presence of parasites and DNAs in the examined tissues. Alterations in the liver with nuclear destruction and cytoplasmic degeneration of infected hepatocytes, presence of inflammatory infiltrates, necrosis of hepatocytes, and changes in splenic architecture and reduction and deformation of white pulp in the spleen were noted. These results indicate a chronic form of visceral leishmaniasis indicating that the hamster is a suitable animal model for the study of pathological features of chronic visceral leishmaniasis caused by L. martiniquensis.


Assuntos
Leishmania/fisiologia , Leishmaniose Visceral/parasitologia , Animais , Cricetinae , Modelos Animais de Doenças , Humanos , Leishmania/genética , Fígado/parasitologia , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Baço/parasitologia
5.
Exp Parasitol ; 216: 107946, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32622941

RESUMO

This study was aimed at investigating the involvement of Receptor for Advanced Glycation End Products (RAGE) during malaria infection and the effects of modulating RAGE on the inflammatory cytokines release and histopathological conditions of affected organs in malarial animal model. Plasmodium berghei (P. berghei) ANKA-infected ICR mice were treated with mRAGE/pAb and rmRAGE/Fc Chimera drugs from day 1 to day 4 post infection. Survival and parasitaemia levels were monitored daily. On day 5 post infection, mice were sacrificed, blood were drawn for cytokines analysis and major organs including kidney, spleen, liver, brain and lungs were extracted for histopathological analysis. RAGE levels were increased systemically during malaria infection. Positive correlation between RAGE plasma concentration and parasitaemia development was observed. Treatment with RAGE related drugs did not improve survival of malaria-infected mice. However, significant reduction on the parasitaemia levels were recorded. On the other hand, inhibition and neutralization of RAGE production during the infection significantly increased the plasma levels of interleukin (IL-4, IL-17A, IL-10 and IL-2) and reduced interferon (IFN)-γ secretion. Histopathological analysis revealed that all treated malarial mice showed a better outcome in histological assessment of affected organs (brain, liver, spleen, lungs and kidney). RAGE is involved in malaria pathogenesis and targeting RAGE could be beneficial in malaria infected host in which RAGE inhibition or neutralization increased the release of anti-inflammatory cytokines (IL-10 and IL-4) and reduce pro-inflammatory cytokine (IFNγ) which may help alleviate tissue injury and improve histopathological conditions of affected organs during the infection.


Assuntos
Citocinas/metabolismo , Malária/imunologia , Malária/patologia , Plasmodium berghei/imunologia , Receptor para Produtos Finais de Glicação Avançada/fisiologia , Animais , Encéfalo/parasitologia , Encéfalo/patologia , Citocinas/sangue , Rim/parasitologia , Rim/patologia , Modelos Lineares , Fígado/parasitologia , Fígado/patologia , Pulmão/parasitologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Parasitemia/imunologia , Distribuição Aleatória , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Receptor para Produtos Finais de Glicação Avançada/sangue , Receptor para Produtos Finais de Glicação Avançada/imunologia , Baço/parasitologia , Baço/patologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-32660993

RESUMO

Previously, ivermectin (1 to 10 mg/kg of body weight) was shown to inhibit the liver-stage development of Plasmodium berghei in orally dosed mice. Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (50% inhibitory concentration [IC50], 10.42 µM) and hypnozoites (IC50, 29.24 µM) in primary macaque hepatocytes when administered as a high dose prophylactically but not when administered in radical cure mode. The safety, pharmacokinetics, and efficacy of oral ivermectin (0.3, 0.6, and 1.2 mg/kg) with and without chloroquine (10 mg/kg) administered for 7 consecutive days were evaluated for prophylaxis or radical cure of P. cynomolgi liver stages in rhesus macaques. No inhibition or delay to blood-stage P. cynomolgi parasitemia was observed at any ivermectin dose (0.3, 0.6, and 1.2 mg/kg). Ivermectin (0.6 and 1.2 mg/kg) and chloroquine (10 mg/kg) in combination were well-tolerated with no adverse events and no significant pharmacokinetic drug-drug interactions observed. Repeated daily ivermectin administration for 7 days did not inhibit ivermectin bioavailability. It was recently demonstrated that both ivermectin and chloroquine inhibit replication of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro Further ivermectin and chloroquine trials in humans are warranted to evaluate their role in Plasmodium vivax control and as adjunctive therapies against COVID-19 infections.


Assuntos
Antimaláricos/farmacologia , Cloroquina/farmacologia , Ivermectina/farmacologia , Fígado/efeitos dos fármacos , Malária/tratamento farmacológico , Plasmodium cynomolgi/efeitos dos fármacos , Animais , Antimaláricos/sangue , Antimaláricos/farmacocinética , Disponibilidade Biológica , Cloroquina/sangue , Cloroquina/farmacocinética , Esquema de Medicação , Combinação de Medicamentos , Sinergismo Farmacológico , Feminino , Hepatócitos/efeitos dos fármacos , Hepatócitos/parasitologia , Ivermectina/sangue , Ivermectina/farmacocinética , Fígado/parasitologia , Macaca mulatta , Malária/parasitologia , Masculino , Parasitemia/tratamento farmacológico , Plasmodium cynomolgi/crescimento & desenvolvimento , Plasmodium cynomolgi/patogenicidade , Cultura Primária de Células , Esquizontes/efeitos dos fármacos , Esquizontes/crescimento & desenvolvimento
7.
Parasitol Res ; 119(10): 3233-3241, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32656658

RESUMO

Anisakid nematode larvae occur frequently in the liver of Atlantic cod, but merely few infection data from cod in waters around Greenland exist. The present study reports the occurrence of third-stage anisakid larvae in the livers of 200 Atlantic cod caught on fishing grounds along the West coast of Greenland (fjord systems of Maniitsoq) in May, June, August and September 2017. Classical and molecular helminthological techniques were used to identify the nematodes. A total of 200 cod livers were examined, and 194 were infected with third-stage nematode larvae (overall prevalence of infection 97%) with a mean intensity of 10.3 (range between 1 and 44 parasites per fish). Prevalences recorded were 96% for Anisakis simplex (s.l.), 55% for Pseudoterranova decipiens (s.l.) and 8% for Contracaecum osculatum (s.l.). Sequencing the mtDNA cox2 from 8 out of 23 these latter larvae conferred these to C. osculatum sp. B. A clear seasonal variation was observed, with a rise in A. simplex (s.l.) and P. decipiens (s.l.) occurrence in June and August and a decline in September. The study may serve as a baseline for future investigations using the three anisakids as biological indicators in Greenland waters.


Assuntos
Anisaquíase/epidemiologia , Anisakis/isolamento & purificação , Doenças dos Peixes/parasitologia , Gadus morhua/parasitologia , Animais , Anisakis/classificação , Anisakis/genética , Oceano Atlântico/epidemiologia , Ciclo-Oxigenase 2/genética , DNA Mitocondrial/genética , Groenlândia/epidemiologia , Larva , Fígado/parasitologia
8.
Exp Parasitol ; 215: 107933, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32525006

RESUMO

Schistosomiasis is still a public health problem. Praziquantel is the only drug available for treatment of all forms of human schistosomiasis. Although praziquantel is an effective drug against all species of human schistosomes, concerns about resistance have been raised, especially in endemic areas. A hybrid compound containing several pharmacophore within a single molecule is a promising strategy. Here, we described the anti-schistosomal effect of 4-(2-Chloroquinolin-3-yl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (PPQ-6), a hybrid drug based on quinoline and pyridine. PPQ-6 was given as two regimens (20 or 40 mg/kg). In both regimens, PPQ-6 significantly reduced liver and spleen indices, nitric oxide production, tissue egg load, hepatic granuloma size and count, immature eggs and total worm burden especially females. Our findings suggested that PPQ-6 is a promising anti-schistosomal agent; however more research is needed to elucidate its mechanism of action and report its activity on juvenile schistosomes and other species of human schistosomes.


Assuntos
Piridinas/farmacologia , Quinolinas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/farmacologia , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Feminino , Fígado/parasitologia , Fígado/patologia , Masculino , Camundongos , Óxido Nítrico/análise , Piridinas/química , Piridinas/uso terapêutico , Quinolinas/química , Quinolinas/uso terapêutico , Distribuição Aleatória , Esquistossomicidas/química , Esquistossomicidas/uso terapêutico , Fatores Sexuais , Baço/parasitologia , Baço/patologia
9.
Parasitol Res ; 119(7): 2139-2147, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32476061

RESUMO

Coccidian parasites of fish have received considerably less attention than their terrestrial counterparts, and within piscine hosts, most studies have focused on freshwater fish. The present study aimed to describe oocyst morphology, phylogenetic affinities, and the impacts of coccidian parasites infecting the internal organs of a commercially valuable marine fish, the blue whiting (Micromesistius poutassou), captured off the Portuguese coast. As part of the phylogenetic analysis, sequences from coccidians infecting the pout (Trisopterus luscus) and the Atlantic chub mackerel (Scomber colias) were included, and the oocyst morphology of the coccidians infecting the former was also reported. Results showed that the prevalence of coccidiosis in the blue whiting was very high (> 82%), occurring in all analyzed organs, despite being more abundant in the liver. A significant negative correlation was found between the abundance of the parasites in the liver and host condition index (p < 0.05), which indicates a negative effect on the fitness of this host. Phylogenetic analyses of the parasites found in all three species examined identified three different species of Goussia, closely related to Goussia clupearum. Adding to previous research, we propose the existence of a fourth group of Goussia, the clupearum type, able to infect multiple organs and phylogenetic related with G. clupearum.


Assuntos
Coccidiose/veterinária , Eimeriidae/classificação , Eimeriidae/patogenicidade , Doenças dos Peixes/parasitologia , Gadiformes/parasitologia , Animais , Coccidiose/parasitologia , Eimeriidae/citologia , Eimeriidae/genética , Fígado/parasitologia , Oocistos/classificação , Oocistos/citologia , Oocistos/genética , Perciformes/parasitologia , Filogenia , Portugal , Alimentos Marinhos/parasitologia
10.
PLoS Negl Trop Dis ; 14(6): e0008421, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32598389

RESUMO

BACKGROUND: The liver fluke, Opisthorchis felineus, is widely distributed throughout Europe and large parts of the Russian Federation. In Western Siberia, information about opisthorchiasis is lacking although infection may lead to severe liver and bile duct diseases. We aimed to assess the current prevalence of O. felineus infection along with associated risk factors and morbidity in rural Western Siberia. METHODS: We conducted a community-based, cross-sectional study in the rural Shegarskiy district, Tomsk Oblast, Russian Federation. All household members (≥ 7 years) present on the survey day were enrolled (n = 600). Two stool samples per person were examined for helminth eggs, using PARASEP (DiaSys Ltd, UK). The number of eggs per gram (EPG) of feces was recorded. Each study participant was interviewed to determine risk factors, using a pre-tested questionnaire. An abdominal ultrasonography examination of liver and bile ducts was performed with a mobile, high resolution ultrasound device. In total, 488 persons completed assessments (two stool samples, completed questionnaires); of those, 436 individuals had an ultrasonography (US) examination. RESULTS: We observed a prevalence of O. felineus infection of 60.2%. Significant risk factors for infection were the consumption of river fish (odds ratio from adjusted analysis [aOR] 2.4, 95% CI 1.52-3.95, p<0.001), particularly stock fish (OR from multivariable analysis [mOR] 3.2, 95% CI 2.63-3.80, p<0.001), smoked fish (mOR 1.5, 95% CI 1.24-1.72, p<0.001), frozen fish (mOR 1.6, 95% CI 1.29-2.02, p<0.001), and raw fish (mOR 1.4, 95% CI 1.05-1.84, p = 0.02); and fishing activities (mOR 1.2, 95% CI 1.03-1.43, p = 0.019). Women had a higher risk of infection than men. Infection was associated positively with age and negatively with socio-economic status. The respondents' general awareness of opisthorchiasis was quite high (93.2%), but their knowledge about infection transmission and prevention was insufficient. Children aged 7-18 years old had a lower level of awareness compared to adults. The abdominal ultrasonography results demonstrated a strong association between O. felineus infection and gallbladder stones (mOR 2.8, 95% CI 1.33-6.04, p = 0.007) and periductal fibrosis of intrahepatic bile ducts (mOR 1.9, 95% CI 1.08-3.46, p = 0.026). CONCLUSION: O. felineus infection is highly prevalent in rural regions of Western Siberia, and associated with severe hepatobiliary pathology. Identified risk factors will be used to develop a comprehensive targeted O. felineus infection control program.


Assuntos
Opistorquíase/epidemiologia , Opisthorchis/patogenicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias dos Ductos Biliares/parasitologia , Ductos Biliares/parasitologia , Criança , Estudos Transversais , Feminino , Peixes/parasitologia , Humanos , Fígado/parasitologia , Masculino , Pessoa de Meia-Idade , Morbidade , Análise Multivariada , Opistorquíase/complicações , Opistorquíase/diagnóstico , Opistorquíase/parasitologia , Prevalência , Fatores de Risco , População Rural , Sibéria/epidemiologia , Ultrassonografia , Adulto Jovem
11.
Parasitol Res ; 119(8): 2631-2640, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32556500

RESUMO

The genus Plasmodium (Plasmodiidae) ranks among the most widespread intracellular protozoan parasites affecting a wide range of mammals, birds, and reptiles. Little information is available about lizard malaria parasites in South America, and the pathological features of the resulting parasitoses remain unknown or poorly understood. To partially fill in these gaps, we conducted blood smear analysis, molecular detection, and phylogenetic and pathological investigations in lizards inhabiting an Atlantic Forest fragment in Paraiba, Brazil. From 104 striped forest whiptails (Kentropyx calcarata) screened for the presence of haemosporidian parasites, 67 (64.4%) were positive. Four of five Amazon lava lizards (Strobilurus torquatus) we collected from this same area were also positive. A total of 27 forest whiptails were infected with a new genetic lineage of Plasmodium kentropyxi and other Plasmodium lineages were also detected. Histopathological analysis in infected forest whiptails revealed systemic intraerythrocytic Plasmodium stages, mainly gametocytes, in the liver, lung, and heart. Also, the liver of infected lizards had mild to moderate levels of Kupffer cell and melanomacrophage hypertrophy/hyperplasia with sinusoid leukocytosis. Overall, our findings suggest that an endemic Plasmodium species causes histological alterations that are not related to major pathological processes in striped forest whiptails.


Assuntos
Lagartos/parasitologia , Plasmodium/genética , Plasmodium/patogenicidade , Infecções Protozoárias em Animais/parasitologia , Animais , Brasil , Eritrócitos/parasitologia , Florestas , Fígado/parasitologia , Fígado/patologia , Filogenia , Plasmodium/classificação , Infecções Protozoárias em Animais/patologia
12.
PLoS Negl Trop Dis ; 14(5): e0007640, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32442168

RESUMO

We present a comprehensive analysis of the hepatic miRNA transcriptome at one month post-infection of experimental primary alveolar echinococcosis (AE), a parasitic infection caused upon ingestion of E. multilocularis eggs. Liver tissues were collected from infected and non-infected C57BL/6 mice, then small RNA libraries were prepared for next-generation sequencing (NGS). We conducted a Stem-loop RT-qPCR for validation of most dysregulated miRNAs. In infected mice, the expression levels of 28 miRNAs were significantly altered. Of these, 9 were up-regulated (fold change (FC) ≥ 1.5) and 19 were down-regulated (FC ≤ 0.66) as compared to the non-infected controls. In infected livers, mmu-miR-148a-3p and mmu-miR-101b-3p were 8- and 6-fold down-regulated, respectively, and the expression of mmu-miR-22-3p was reduced by 50%, compared to non-infected liver tissue. Conversely, significantly higher hepatic levels were noted for Mus musculus (mmu)-miR-21a-5p (FC = 2.3) and mmu-miR-122-5p (FC = 1.8). In addition, the relative mRNA expression levels of five genes (vegfa, mtor, hif1-α, fasn and acsl1) that were identified as targets of down-regulated miRNAs were significantly enhanced. All the five genes exhibited a higher expression level in livers of E. multilocularis infected mice compared to non-infected mice. Finally, we studied the issue related to functionally mature arm selection preference (5p and/or 3p) from the miRNA precursor and showed that 9 pre-miRNAs exhibited different arm selection preferences in normal versus infected liver tissues. In conclusion, this study provides first evidence that miRNAs are regulated early in primary murine AE. Our findings raise intriguing questions such as (i) how E. multilocularis affects hepatic miRNA expression;(ii) what are the alterations in miRNA expression patterns in more advanced AE-stages; and (iii) which hepatic cellular, metabolic and/or immunologic processes are modulated through altered miRNAs in AE. Thus, further research on the regulation of miRNAs during AE is needed, since miRNAs constitute an attractive potential option for development of novel therapeutic approaches against AE.


Assuntos
Equinococose/genética , Echinococcus multilocularis/fisiologia , Fígado/metabolismo , MicroRNAs/metabolismo , Óvulo/crescimento & desenvolvimento , Animais , Equinococose/metabolismo , Equinococose/parasitologia , Echinococcus multilocularis/crescimento & desenvolvimento , Feminino , Humanos , Fígado/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Óvulo/fisiologia
13.
Rev Bras Parasitol Vet ; 29(2): e002420, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428179

RESUMO

Hepatozoon pyramidumi sp. n. is described from the blood of the Egyptian saw-scaled viper, Echis pyramidum, captured from Saudi Arabia. Five out of ten viper specimens examined (50%) were found infected with Hepatozoon pyramidumi sp. n. with parasitaemia level ranged from 20-30%. The infection was restricted only to the erythrocytes. Two morphologically different forms of intraerythrocytic stages were observed; small and mature gamonts. The small ganomt with average size of 10.7 × 3.5 µm. Mature gamont was sausage-shaped with recurved poles measuring 16.3 × 4.2 µm in average size. Infected erythrocytes were hypertrophied; their nuclei were deformed and sometimes displaced from their central position in the normal uninfected cell. Merogonic stages were observed in the lung endothelial cell and the liver parenchyma cells. Mature meront was 17.8 × 13.6 µm and contained banana-shaped merozoites with average size of ~15 × 2 µm. Phylogenetic analysis based on the SSU rDNA sequence clustered Hepatozoon pyramidumi sp. n with previously sequenced Hepatozoon spp., most of them infected reptilian hosts without geographic consideration. The morphological and molecular comparison with closely related species proved the taxonomic uniqueness and novelty of the present form.


Assuntos
Apicomplexa/genética , Apicomplexa/fisiologia , DNA de Protozoário/genética , Viperidae/parasitologia , Animais , Apicomplexa/classificação , DNA Ribossômico/genética , Eritrócitos/parasitologia , Eritrócitos/patologia , Fígado/parasitologia , Fígado/patologia , Pulmão/parasitologia , Pulmão/patologia , Parasitemia/parasitologia , Parasitemia/veterinária , Filogenia , Arábia Saudita , Análise de Sequência de DNA , Viperidae/sangue
14.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(3): 255-261, 2020 May 07.
Artigo em Chinês | MEDLINE | ID: mdl-32468787

RESUMO

OBJECTIVE: To investigate the effect of gender on hepatic pathology and antibody-mediated immunity in Schistosoma japonicum-infected C57BL/6 mice. METHODS: Female and male C57BL/6 mice were infected with S. japonicum, and the hepatic pathological changes were observed using HE and picrosirius red staining in mice 8 weeks post-infection. The serum specific IgG antibody levels against the soluble adult worm antigen (SWA) and soluble egg antigen (SEA) were measured in mice using enzyme-linked immunosorbent assay (ELISA), and the percentages of follicular helper T (Tfh) cells and regulatory T (Treg) cells were detected in mouse spleen and lymph nodes using flow cytometry. RESULTS: HE staining showed no significant difference in the mean area of a single hepatic egg granuloma between female and male mice 8 weeks post-infection with S. japonicum [(28.050 ± 3.576) × 104 µm2 vs. (26.740 ± 4.093) × 104 µm2; t = 0.241, P = 0.821], and picrosirius red staining revealed no statistical differences between female and male mice in terms of the mean proportion of picrosirius red stained hepatic tissues [(7.667 ± 1.856)% vs. (7.667 ± 1.764)%; t = 0, P = 1] or the mean optical density [(0.023 ± 0.003) vs. (0.027 ± 0.007); t = 0.447, P = 0.678]. ELISA detected no significant differences in the serum IgG antibody levels against SWA [(2.098 ± 0.037) vs. (1.970 ± 0.071); t = 1.595, P = 0.162] or SEA [(3.738 ± 0.039) vs. (3.708 ± 0.043); t = 0.512, P = 0.623] between female and male mice 8 weeks post-infection with S. japonicum. Flow cytometry detected significantly greater percentages of Tfh cells in the spleen [female mice, (8.645 ± 1.356)% vs. (1.730 ± 0.181)%, t = 5.055, P = 0.002; male mice, (8.470 ± 1.161)% vs. (1.583 ± 0.218)%, t = 5.829, P = 0.001] and lymph nodes [female mice, (3.218 ± 0.153)% vs. (1.095 ± 0.116)%, t = 11.040, P < 0.001; male mice, (3.673 ± 0.347)% vs. (0.935 ± 0.075)%, t = 8.994, P = 0.001) of both female and male mice 8 weeks post-infection with S. japonicum than in uninfected mice; however, no significant differences were seen between female and male mice 8 weeks post-infection with S. japonicum in terms of the percentages of Tfh cells in the spleen [(8.645 ± 1.356)% vs. (8.470 ± 1.161)%; t = 0.098, P = 0.925] or lymph nodes [(3.218 ± 0.153)% vs. (3.673 ± 0.347)%; t = 1.332, P = 0.241]. There was no significant difference in the proportion of Treg cells in the spleen of male mice between infected and uninfected mice [(10.060 ± 0.361)% vs. (10.130 ± 0.142)%; t = 0.174, P = 0.867], while a higher proportion of Treg cells was seen in the spleen of female mice 8 weeks post-infection with S. japonicum than in uninfected mice [(10.530 ± 0.242)% vs. (9.450 ± 0.263)%; t = 3.021, P = 0.023]. There was no significant difference in the proportion of Treg cells in the spleen between female and male mice infected with S. japonicum [(10.530 ± 0.242)% vs. (10.060 ± 0.361)%; t =1.077, P = 0.323]. In addition, the proportions of Treg cells were significantly greater in the lymph node of S. japonicum -infected female [(17.150 ± 0.805)% vs. (13.100 ± 0.265)%; t = 4.781, P = 0.003] and male mice [(18.550 ± 0.732)% vs. (12.630 ± 0.566)%; t = 6.402, P = 0.001] than in uninfected mice; however, no significant difference was seen between female and male mice 8 weeks post-infection [(17.150 ± 0.805)% vs. (18.550 ± 0.732)%; t = 1.287, P = 0.246]. CONCLUSIONS: There are no gender-specific hepatic pathological changes or antibody-mediated immunity in C57BL/6 mice post-infection with S. japonicum.


Assuntos
Esquistossomose Japônica , Animais , Anticorpos/sangue , Feminino , Fígado/imunologia , Fígado/parasitologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Schistosoma japonicum , Esquistossomose Japônica/imunologia , Esquistossomose Japônica/patologia , Fatores Sexuais , Linfócitos T Reguladores/imunologia
15.
Cesk Patol ; 56(1): 32-34, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32393044

RESUMO

Echinococcus multilocularis causes an aggressive form of hydatidosis whose histomorphological picture is generally not well recognized. We report a case of 39-year-old women presenting with poorly circumscribed nodules in the right hepatic lobe. Owing to the clinical suspicion of focal nodular hyperplasia and hepatocellular adenoma, a core biopsy was performed. The histological findings of necrotic fibrous tissue infiltrated by narrow epithelial cords and small cysts containing cytokeratin positive material were in concordance with the diagnosis of cholangiocarcinoma. Subsequent examination of the surgically resected necrotic nodules with a vital tissue at the periphery corresponded to a reparative fibrosis accompanied by a striking ductular proliferation. Serological and molecular genetic work-up led to the diagnosis of Echinococcus multilocularis. The aim of this report is to point out the unusual histological features of the solid foci of alveolar hydatidosis, which consisted of necrotic fibrous tissue with ductular reaction. Such findings in a core biopsy may simulate regressively altered carcinoma.


Assuntos
Equinococose , Echinococcus multilocularis , Hiperplasia Nodular Focal do Fígado , Fígado , Adulto , Animais , Biópsia , Equinococose/diagnóstico , Echinococcus multilocularis/isolamento & purificação , Feminino , Hiperplasia Nodular Focal do Fígado/diagnóstico , Humanos , Fígado/parasitologia
16.
J Parasitol ; 106(2): 268-275, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32294758

RESUMO

Gambusia affinis (western mosquitofish) serves as a host for a variety of larval and adult parasites. Gambusia affinis is also an incipient matrotroph, exhibiting adjustments in post-fertilization provisioning to some offspring within a brood using recently acquired resources. Nutrient transfer to embryos is expected to limit the loss of embryo mass during development resulting in larger offspring. Since larger offspring are more likely to survive, maternal contributions are expected to increase fitness. The presence of parasites, particularly intestinal helminths, potentially reduces body condition and resources available for developing offspring, thereby reducing host fitness. The effects of parasitism on the fitness of G. affinis were investigated in the present study. Fish were collected from 3 sites monthly from June 2015 through August 2016. All helminth parasites were collected during necropsy and identified. Brood size and embryo developmental stage were recorded for each female fish. Additionally, 10 ova/embryos of each developmental stage from each female fish collected from May through August 2016 were haphazardly selected and individually weighed. From 429 female mosquitofish, 5,072 helminths were collected. Brood size varied among collection sites and was positively influenced by maternal body condition, the number of daylight hours, water temperature, and the intensity of both plerocercoid and adult Schyzocotyle acheilognathi. However, brood size was negatively related to the intensity of Neoechinorhynchus cylindratus cystacanth and an increasing number of days between collection and dissection. Embryo weight increased with the presence of either Camallanidae or Contracaecum multipapulatum, embryo developmental stage, and relative host density. These results indicate that some parasitic helminth species negatively affect the fitness of G. affinis, while some positively affect fitness, and that effect can vary with intensity.


Assuntos
Acantocéfalos/fisiologia , Ciprinodontiformes/parasitologia , Doenças dos Peixes/parasitologia , Helmintíase Animal/parasitologia , Animais , Infecções por Ascaridida/parasitologia , Infecções por Ascaridida/veterinária , Ascaridoidea/fisiologia , Ciprinodontiformes/embriologia , Ciprinodontiformes/fisiologia , Feminino , Modelos Lineares , Fígado/parasitologia , Fígado/patologia , Distribuição Normal , Fotoperíodo , Reprodução , Estações do Ano , Temperatura
17.
Parasit Vectors ; 13(1): 109, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111243

RESUMO

BACKGROUND: Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons. METHODS: Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies. RESULTS: Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. CONCLUSIONS: Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.


Assuntos
Coinfecção/patologia , Coinfecção/veterinária , Hepatopatias Parasitárias/patologia , Hepatopatias Parasitárias/veterinária , Esquistossomose/patologia , Esquistossomose/veterinária , Tricuríase/patologia , Tricuríase/veterinária , Doenças dos Animais/parasitologia , Doenças dos Animais/patologia , Animais , Doença Crônica , Coinfecção/parasitologia , Feminino , Granuloma/patologia , Humanos , Fígado/metabolismo , Fígado/parasitologia , Fígado/patologia , Hepatopatias Parasitárias/parasitologia , Masculino , Papio , Contagem de Ovos de Parasitas , Projetos Piloto , Primatas , Schistosoma mansoni , Esquistossomose/parasitologia , Transcriptoma , Tricuríase/parasitologia , Trichuris
18.
Parasit Vectors ; 13(1): 146, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32188510

RESUMO

BACKGROUND: The East Route Project (ERP) of the South-to-North Water Diversion Project (SNWDP) stretches across schistosomiasis endemic and non-endemic areas in China, which may lead to the dispersal of Oncomelania hupensis, the intermediate host of Schistosoma japonicum, from permissive areas along the Yangtze River Basin to non-permissive areas in northern China. A previous survey demonstrated that O. hupensis could survive and breed for 13 years (12 generations) after being transferred to a non-permissive area, and could be infected by S. japonicum. However, it is not clear if the migrated snails will change their ability to transmit S. japonicum. METHODS: We infected mice with the cercariae released from the infected transferred snails bred in Jining city of Shandong Province (non-permissive areas) for 13 years. The mice in the control group were infected with cercariae derived from the snails collected in their original habitat (Jiangdu county of Jiangsu Province, permissive areas). Then, we explored the pathogenicity to mice including worm burden, liver egg count and pathology. Additionally, the gene expression profiles of the adult male and female worms recovered from the infected mice were analyzed by RNA sequencing. RESULTS: The worm burden, liver egg count and pathology of the mice infected with cercariae released from transferred snails bred in non-permissive areas for 13 years showed no significant differences, when compared with the control cercariae. Slight changes occurred at the transcription level between adult male and female worms recovered from mice infected with cercariae derived from snails bred in permissive and non-permissive areas. Only fourteen genes were significantly differentially expressed in the comparison of adult female worms, and no significantly differentially expressed gene was found in the comparison of adult male worms. CONCLUSIONS: Our findings strongly suggest that transferred snails did not change their schistosomiasis transmission ability and the worms derived from them retained the original pathogenicity, even after migrating from permissive to non-permissive areas for 13 years. Therefore, a long-term surveillance system of snails along the SNWDP is urgently needed to prevent the diffusion of O. hupensis and reduce the risk of transmission of schistosomiasis.


Assuntos
Cercárias/genética , Gastrópodes/parasitologia , Schistosoma japonicum/genética , Esquistossomose Japônica/transmissão , Animais , Comportamento Animal , Cercárias/patogenicidade , China , Feminino , Fígado/parasitologia , Fígado/patologia , Masculino , Camundongos , Carga Parasitária , Schistosoma japonicum/patogenicidade , Fatores de Tempo
19.
Malar J ; 19(1): 113, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183833

RESUMO

BACKGROUND: New strategies are needed to reduce the incidence of malaria, and promising approaches include the development of vaccines and monoclonal antibodies (mAbs) that target the circumsporozoite protein (CSP). To select the best candidates and speed development, it is essential to standardize preclinical assays to measure the potency of such interventions in animal models. METHODS: Two assay configurations were studied using transgenic Plasmodium berghei expressing Plasmodium falciparum full-length circumsporozoite protein. The assays measured (1) reduction in parasite infection of the liver (liver burden) following an intravenous (i.v) administration of sporozoites and (2) protection from parasitaemia following mosquito bite challenge. Two human CSP mAbs, AB311 and AB317, were compared for their ability to inhibit infection. Multiple independent experiments were conducted to define assay variability and resultant impact on the ability to discriminate differences in mAb functional activity. RESULTS: Overall, the assays produced highly consistent results in that all individual experiments showed greater functional activity for AB317 compared to AB311 as calculated by the dose required for 50% inhibition (ID50) as well as the serum concentration required for 50% inhibition (IC50). The data were then used to model experimental designs with adequate statistical power to rigorously screen, compare, and rank order novel anti-CSP mAbs. CONCLUSION: The results indicate that in vivo assays described here can provide reliable information for comparing the functional activity of mAbs. The results also provide guidance regarding selection of the appropriate experimental design, dose selection, and group sizes.


Assuntos
Anticorpos Monoclonais/imunologia , Parasitemia/prevenção & controle , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Antiprotozoários/sangue , Modelos Animais de Doenças , Feminino , Concentração Inibidora 50 , Fígado/parasitologia , Malária Falciparum/imunologia , Malária Falciparum/terapia , Camundongos , Camundongos Endogâmicos C57BL , Organismos Geneticamente Modificados , Carga Parasitária , Plasmodium berghei/genética , Plasmodium falciparum/genética , Proteínas de Protozoários/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-32179499

RESUMO

Liver flukes include Fasciola hepatica, Fasciola gigantica, Clonorchis sinensis, Opisthorchis spp., Fascioloides magna, Gigantocotyle explanatum and Dicrocoelium spp. The two main species, F. hepatica and F. gigantica, are major parasites of livestock and infections result in huge economic losses. As with C. sinensis, Opisthorchis spp. and Dicrocoelium spp., they affect millions of people worldwide, causing severe health problems. Collectively, the group is referred to as the Food-Borne Trematodes and their true significance is now being more widely recognised. However, reports of resistance to triclabendazole (TCBZ), the most widely used anti-Fasciola drug, and to other current drugs are increasing. This is a worrying scenario. In this review, progress in understanding the mechanism(s) of resistance to TCBZ is discussed, focusing on tubulin mutations, altered drug uptake and changes in drug metabolism. There is much interest in the development of new drugs and drug combinations, the re-purposing of non-flukicidal drugs, and the development of new drug formulations and delivery systems; all this work will be reviewed. Sound farm management practices also need to be put in place, with effective treatment programmes, so that drugs can be used wisely and their efficacy conserved as much as is possible. This depends on reliable advice being given by veterinarians and other advisors. Accurate diagnosis and identification of drug-resistant fluke populations is central to effective control: to determine the actual extent of the problem and to determine how well or otherwise a treatment has worked; for research on establishing the mechanism of resistance (and identifying molecular markers of resistance); for informing treatment options; and for testing the efficacy of new drug candidates. Several diagnostic methods are available, but there are no recommended guidelines or standardised protocols in place and this is an issue that needs to be addressed.


Assuntos
Anti-Helmínticos/farmacologia , Resistência a Medicamentos , Fasciola hepatica/efeitos dos fármacos , Fígado/parasitologia , Animais , Benzimidazóis/farmacologia , Fasciola hepatica/classificação , Fasciolíase/diagnóstico , Fasciolíase/tratamento farmacológico , Fasciolíase/parasitologia , Triclabendazol/farmacologia
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