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1.
Parasites Hosts Dis ; 62(2): 243-250, 2024 May.
Article in English | MEDLINE | ID: mdl-38835265

ABSTRACT

We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (n=5 each) were orally administered 1,000 T. canis 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (n=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with T. canis exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of T. canis larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to T. canis infection in mice, which may have implications to further understand human toxocariasis.


Subject(s)
Brain , Cytokines , Larva , Liver , Lung , Mice, Inbred BALB C , Toxocara canis , Toxocariasis , Animals , Toxocara canis/immunology , Toxocariasis/immunology , Toxocariasis/pathology , Toxocariasis/parasitology , Larva/immunology , Mice , Cytokines/metabolism , Lung/parasitology , Lung/immunology , Lung/pathology , Liver/parasitology , Liver/pathology , Liver/immunology , Brain/parasitology , Brain/immunology , Brain/pathology , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/parasitology , Female , Parasite Load , Eye/parasitology , Eye/immunology , Eye/pathology , Disease Models, Animal
2.
Front Immunol ; 15: 1279043, 2024.
Article in English | MEDLINE | ID: mdl-38840916

ABSTRACT

Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas. There is a need for new therapeutic drugs and alternative drug treatments for schistosomiasis. The current study hypothesized that cysteinyl leukotrienes (cysLTs) could mediate fibroproliferative pathology during schistosomiasis. Cysteinyl leukotrienes (cysLTs) are potent lipid mediators that are known to be key players in inflammatory diseases, such as asthma and allergic rhinitis. The present study aimed to investigate the role of cysLTR1 during experimental acute and chronic schistosomiasis using cysLTR1-/- mice, as well as the use of cysLTR1 inhibitor (Montelukast) to assess immune responses during chronic Schistosoma mansoni infection. Mice deficient of cysLTR1 and littermate control mice were infected with either high or low dose of Schistosoma mansoni to achieve chronic or acute schistosomiasis, respectively. Hepatic granulomatous inflammation, hepatic fibrosis and IL-4 production in the liver was significantly reduced in mice lacking cysLTR1 during chronic schistosomiasis, while reduced liver pathology was observed during acute schistosomiasis. Pharmacological blockade of cysLTR1 using montelukast in combination with PZQ reduced hepatic inflammation and parasite egg burden in chronically infected mice. Combination therapy led to the expansion of Tregs in chronically infected mice. We show that the disruption of cysLTR1 is dispensable for host survival during schistosomiasis, suggesting an important role cysLTR1 may play during early immunity against schistosomiasis. Our findings revealed that the combination of montelukast and PZQ could be a potential prophylactic treatment for chronic schistosomiasis by reducing fibrogranulomatous pathology in mice. In conclusion, the present study demonstrated that cysLTR1 is a potential target for host-directed therapy to ameliorate fibrogranulomatous pathology in the liver during chronic and acute schistosomiasis in mice.


Subject(s)
Acetates , Cyclopropanes , Disease Models, Animal , Mice, Knockout , Quinolines , Receptors, Leukotriene , Schistosomiasis mansoni , Sulfides , Animals , Receptors, Leukotriene/metabolism , Mice , Cyclopropanes/therapeutic use , Cyclopropanes/pharmacology , Acetates/therapeutic use , Acetates/pharmacology , Sulfides/therapeutic use , Sulfides/pharmacology , Schistosomiasis mansoni/drug therapy , Schistosomiasis mansoni/immunology , Schistosomiasis mansoni/parasitology , Quinolines/therapeutic use , Quinolines/pharmacology , Female , Schistosoma mansoni/immunology , Chronic Disease , Leukotriene Antagonists/pharmacology , Leukotriene Antagonists/therapeutic use , Liver/parasitology , Liver/pathology , Liver/metabolism , Liver/immunology , Mice, Inbred C57BL , Praziquantel/therapeutic use , Praziquantel/pharmacology , T-Lymphocytes, Regulatory/immunology
3.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(2): 137-147, 2024 May 15.
Article in Chinese | MEDLINE | ID: mdl-38857956

ABSTRACT

OBJECTIVE: To screen differentially expressed long non-coding RNAs (lncRNAs) in the liver of mice infected with Schistosoma japonicum during the chronic pathogenic stage and identify their functions, so as to provide insights into unravelling the role of lncRNAs in S. japonicum infection-induced liver disorders. METHODS: Twenty 6-week-old C57BL/6 mice were randomly divided into two groups, of 10 animals each group. Each mouse in the experimental group was infected with (15 ± 2) S. japonicum cercariae via the abdomen for modeling chronic S. japonicum infection in mice, and distilled water served as controls. All mice were sacrificed 70 days post-infection, and mouse liver specimens were sampled for RNA extraction and library construction. All libraries were sequenced on the Illumina NovaSeq 6000 sequencing platform. Data cleaning was performed using the fastp software, and reference genome alignment and gene expression (FPKM) calculation were performed using the HISAT2 software. Potential lncRNA sequences were predicted using the software CNIC, CPC, Pfam, and PLEK, and potential lncRNAs were screened. Differentially expressed lncRNAs were screened with the DESeq2 software and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to identify biological processes and metabolic pathways involved in target genes of differentially expressed lncRNAs. RESULTS: A total of 333 potential lncRNAs were screened, and 67 were identified as differentially expressed lncRNAs, including 49 up-regulated and 18 down-regulated lncRNAs. A total of 53 target genes were predicted for differentially expressed lncRNAs. GO enrichment analysis showed that these target genes were mainly enriched in biological process and molecular function, among which Sema7a, Arrb1, and Ccl21b genes may be hub target genes for positive regulation of extracellular regulated protein kinase 1 (ERK1) and ERK2 cascades and may participate in the regulation of collagen expression. KEGG enrichment analysis showed that the target genes of differentially expressed lncRNAs were mainly enriched in cytokine-cytokine receptor interaction, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear factor kappa-B (NF-κB) signaling pathway. CONCLUSIONS: This study identifies differentially expressed lncRNAs and functional enrichment of their target genes in the liver of mice during the chronic pathogenic stage of S. japonicum infection. Up-regulated lncRNAs may affect biological processes of ERK1/2 cascades and chemokine signaling pathways via target genes Sema7a, Arrb1, and Ccl21b, thereby affecting collagen expression and inflammatory signal pathways, ultimately affecting the development of liver disorders.


Subject(s)
Liver , Mice, Inbred C57BL , RNA, Long Noncoding , Schistosoma japonicum , Schistosomiasis japonica , Animals , Schistosomiasis japonica/parasitology , RNA, Long Noncoding/genetics , Mice , Schistosoma japonicum/physiology , Schistosoma japonicum/genetics , Liver/parasitology , Liver/metabolism , Gene Expression Profiling , Chronic Disease , Female
4.
Parasitol Res ; 123(6): 236, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856927

ABSTRACT

Echinococcosis is a worldwide disease endemic to the western region of China. In 2023, echinococcosis was detected in one of 27 wild boars (Sus scrofa) in Yili Prefecture, Xinjiang, northwestern China. Histopathological staining and full sequence mitochondrial (mt) analysis were used to determine the infection genotype. Echinococcus granulosus was detected in the wild boar liver, and the cystic lesion characteristics indicated the E. granulosus genotype (G1). This case is the first confirmation of wild boar serving as a transmitter for the G1 genotype of E. granulosus within China. These findings suggest that surveillance is needed to assess the risk of E. granulosus sensu lato transmission to humans and wild animals.


Subject(s)
Echinococcosis , Echinococcus granulosus , Genotype , Sus scrofa , Swine Diseases , Animals , China , Echinococcus granulosus/genetics , Echinococcus granulosus/isolation & purification , Echinococcus granulosus/classification , Sus scrofa/parasitology , Swine Diseases/parasitology , Swine , Echinococcosis/veterinary , Echinococcosis/parasitology , Echinococcosis/epidemiology , Liver/parasitology , Liver/pathology , Sequence Analysis, DNA , DNA, Mitochondrial/genetics , DNA, Helminth/genetics , Phylogeny
5.
J Med Primatol ; 53(3): e12712, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38825748

ABSTRACT

BACKGROUND: Platynosomiasis in non-human primates kept under human care causes chronic disease of the bile ducts and liver, which initially presents with nonspecific signs and can culminate in the death of the animal. Diagnosing this disease is a challenge, and an ultrasound examination can be an excellent tool when it is suspected. METHODS: This study describes the ultrasound findings from 57 marmosets with suspected infection by Platynosomum sp., the correlated hepatobiliary changes, and the anatomopathological findings that confirmed the occurrence of platynosomiasis. RESULTS: In six marmosets (one C. aurita, two C. jacchus, and three Callithrix sp.), Platynosomum infection was confirmed macroscopically (presence of adult trematodes in the gallbladder) and microscopically (adults, larvae, and eggs in histological examinations and eggs in bile and feces). These findings were compatible with the hepatobiliary changes and with images suggestive of parasitic structures in ante-mortem assessments. CONCLUSION: Ultrasound examination demonstrated its usefulness within the clinical routine for investigating this parasitosis.


Subject(s)
Monkey Diseases , Trematode Infections , Ultrasonography , Animals , Ultrasonography/veterinary , Ultrasonography/methods , Monkey Diseases/diagnostic imaging , Monkey Diseases/parasitology , Monkey Diseases/pathology , Monkey Diseases/diagnosis , Trematode Infections/veterinary , Trematode Infections/diagnostic imaging , Trematode Infections/diagnosis , Trematode Infections/parasitology , Trematode Infections/pathology , Male , Female , Callithrix , Liver/pathology , Liver/diagnostic imaging , Liver/parasitology
6.
Vet Parasitol Reg Stud Reports ; 51: 101021, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38772638

ABSTRACT

Cystic echinococcosis (CE) causes significant losses in Andean livestock production and affects Andean food security. However, more studies are needed to understand the epidemiology of the disease. In addition, the potential contribution of Andean cattle to the transmission of Echinococcus granulosus sensu lato needs to be known. This study aimed to determine the CE-prevalence and its association with risk factors, such as age and sex of the animals, the parasite load (number of cysts/organ) of condemned organs, and the viability and fertility of Echinococcus cysts from cattle in the Andes. The prevalence was examined in 348 cattle from an authorized slaughterhouse of Huancayo at 3300 m altitude. Cyst burden was determined by extracting all cysts from the total of the CE-infected organs. Cyst fertility and protoscolices viability were analysed from 90 randomly selected CE-infected organs. The CE prevalence was 35.6% (124/348; 95% CI: 30.6%-40.6%). There was no significant effect of age and sex on CE prevalence. CE was significantly more prevalent (p < 0.05) in lungs than livers, 34.8% (121/348; 95% CI: 29.8%-39.8%) vs 8.9% (31/348; 95% CI: 5.9%-11.9%). Most (75%) infected organs had one to five cysts. The mean cyst burden was significantly (p = 0.018) higher in the lungs than livers, 6.4 ± 4.9 vs 3.7 ± 2.9. Cyst fertility was 1.6% (10/608; 95% CI: 0.6%-2.6%). Despite the high CE prevalence, infected organs from Andean cattle play a minor role in CE transmission to dogs in the central Peruvian Andes.


Subject(s)
Cattle Diseases , Echinococcosis , Echinococcus granulosus , Animals , Cattle , Peru/epidemiology , Cattle Diseases/epidemiology , Cattle Diseases/parasitology , Cattle Diseases/transmission , Echinococcosis/epidemiology , Echinococcosis/veterinary , Echinococcosis/transmission , Male , Prevalence , Female , Echinococcus granulosus/isolation & purification , Risk Factors , Endemic Diseases/veterinary , Liver/parasitology , Lung/parasitology
7.
Cir Cir ; 92(2): 267-270, 2024.
Article in English | MEDLINE | ID: mdl-38782397

ABSTRACT

Hilar cavernous transformation is the formation of venous structures rich in collateral around the portal vein. Portal vein thrombosis is a rare entity. Although there are many reasons for its etiology, few cases have been reported secondary to hydatid cysts in the liver. Here, we present a 24-year-old patient with complaints of abdominal pain and swelling. Her CT and MRI scans show cholelithiasis with portal vein thrombosis and hilar cavernous transformation due to giant hydatid cyst compression in the lateral liver sector.


La transformación cavernosa hiliar es la formación de estructuras venosas ricas en colaterales alrededor de la vena porta. La trombosis de la vena porta es una afección poco frecuente. Aunque existen muchas razones en su etiología, se han descrito pocos casos secundarios a quiste hidatídico en el hígado. Aquí se presenta el caso de una paciente de 24 años con quejas de dolor abdominal e hinchazón. La tomografía computarizada y la resonancia magnética mostraron colelitiasis con trombosis de la vena porta y transformación cavernosa hiliar por compresión del quiste hidatídico gigante en el sector lateral del hígado.


Subject(s)
Echinococcosis, Hepatic , Portal Vein , Humans , Echinococcosis, Hepatic/complications , Echinococcosis, Hepatic/diagnostic imaging , Echinococcosis, Hepatic/surgery , Female , Portal Vein/diagnostic imaging , Young Adult , Tomography, X-Ray Computed , Venous Thrombosis/etiology , Venous Thrombosis/diagnostic imaging , Cholelithiasis/complications , Cholelithiasis/surgery , Cholelithiasis/diagnostic imaging , Magnetic Resonance Imaging , Abdominal Pain/etiology , Liver/parasitology , Liver/diagnostic imaging
8.
Parasit Vectors ; 17(1): 232, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769548

ABSTRACT

BACKGROUND: Schistosoma japonicum eggs lodge in the liver and induce a fibrotic granulomatous immune response in the liver of host. Galectin 3 (Gal-3) is a protein implicated in fibrosis in multiple organs. However, the pathology and molecular mechanisms promoting hepatic granuloma formation remain poorly understood. METHODS: To investigate the effect of blocking galectin-receptor interactions by α-lactose on liver immunopathology in mice with S. japonicum infection, C57BL/6 mice were infected with S. japonicum and alpha (α)-lactose was intraperitoneally injected to block the interactions of galectins and their receptors. RESULTS: Compared with S. japonicum-infected mice, there were significantly decreased Gal-3 mRNA and protein expression levels, decreased intensity of Gal-3 fluorescence in the liver, decreased serum ALT and AST levels, decreased egg numbers of S. japonicum in the liver section, attenuated hepatic and spleen pathology, and alleviated liver fibrosis accompanied with decreased protein expression levels of fibrosis markers [α-smooth muscle actin (α-SMA), collagen I, and collagen IV] in the liver of S. japonicum-infected mice blocked galectin-receptor interactions with hematoxylin-eosin staining, Masson's trichrome staining, immunohistochemistry, or Western blot analysis. Compared with S. japonicum-infected mice, blocking galectin-receptor interactions led to increased eosinophil infiltration and higher eosinophil cationic protein (ECP) expression in the liver, accompanied by increased mRNA levels of eosinophil granule proteins [ECP and eosinophil peroxidase (EPO)], IL-5, CCL11, and CCR3 in the liver and decreased mRNA levels of Gal-3 and M2 macrophage cytokines (TGF-ß, IL-10, and IL-4) in the liver and spleen by using quantitative real-time reverse transcription-polymerase chain reaction. In addition, there were increased Beclin1 protein expression and protein expression ratio of LC3B-II/LC3B-I and decreased p62 protein expression and protein expression ratios of phospho-mTOR/mTOR and phospho-AKT/AKT by Western blot; increased double-labeled F4/80+/LC3B+ cells by immunofluorescence staining; increased M1 macrophage polarization in the liver of S. japonicum-infected mice blocked galectin-receptor interactions by flow cytometric analysis and immunofluorescence staining. CONCLUSIONS: Our data found that blockage of galectin-receptor interactions downregulated Gal-3, which in turn led to reduced liver functional damage, elevated liver eosinophil recruitment, promoted macrophage autophagy through the Akt/mTOR signaling pathway, and alleviated liver pathology and fibrosis. Therefore, Gal-3 plays a pivotal role during S. japonicum infection and could be a target of pharmacologic potential for liver fibrosis induced by S. japonicum infection.


Subject(s)
Galectin 3 , Liver Cirrhosis , Mice, Inbred C57BL , Schistosoma japonicum , Schistosomiasis japonica , Animals , Schistosomiasis japonica/parasitology , Schistosomiasis japonica/complications , Liver Cirrhosis/parasitology , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Mice , Galectin 3/metabolism , Galectin 3/genetics , Liver/parasitology , Liver/pathology , Liver/metabolism , Female , Lactose/pharmacology , Lactose/analogs & derivatives , Galectins/metabolism , Galectins/genetics
9.
Infect Immun ; 92(6): e0002624, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38767360

ABSTRACT

Schistosomiasis is a serious public health problem, and previous studies found that liver function and hepatic cells are damaged. To evaluate the serum parameters of liver function and fibrosis in schistosomiasis patients infected with Schistosoma japonicum (Schistosoma J.) and analyze the correlations between liver function and serum fibrosis markers in patients infected with Schistosoma J., this retrospective study enrolled 133 patients. The study population was divided into four groups: healthy people control group (n = 20), chronic schistosomiasis without liver cirrhosis (CS) group (n = 21), schistosomiasis cirrhosis without hypoalbuminemia (SC-HA) group (n = 68), and schistosomiasis cirrhosis with hypoalbuminemia (SC +HA) group (n = 24). Clinical and laboratory data were collected for analysis. In the multiple comparison of abnormal rates of aspartate aminotransferase (AST) and total bilirubin (TBIL), the abnormal rate of the SC +HA group was significantly higher than that of the other three groups (P < 0.05), and the abnormal rate of γ-GT in the SC +HA group was significantly higher than that in the control group (P < 0.05). Multiple comparison results of serum levels of fibrosis markers showed that the SC group had a significantly higher level of indexes than other groups (P < 0.05). The levels of TGF-ß1 in the CS group, SC-HA group and SC +HA group were significantly higher than those in the control group (P < 0.001). Our study demonstrated that the liver function and hepatic cells were damaged with the progression of liver disease in patients infected with Schistosoma J., and they played an important role in the occurrence and development of liver fibrosis.


Subject(s)
Hepatocytes , Liver Cirrhosis , Schistosoma japonicum , Schistosomiasis japonica , Humans , Liver Cirrhosis/pathology , Liver Cirrhosis/parasitology , Schistosomiasis japonica/complications , Schistosomiasis japonica/pathology , Male , Female , Middle Aged , Animals , Adult , Retrospective Studies , Hepatocytes/pathology , Hepatocytes/parasitology , Biomarkers/blood , Aged , Liver/pathology , Liver/parasitology , Liver Function Tests
10.
Parasitol Res ; 123(5): 215, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771511

ABSTRACT

Schistosomiasis is a neglected tropical disease associated with considerable morbidity. Praziquantel (PZQ) is effective against adult schistosomes, yet, it has little effect on juvenile stages, and PZQ resistance is emerging. Adopting the drug repurposing strategy as well as assuming enhancing the efficacy and lessening the doses and side effects, the present study aimed to investigate the in vivo therapeutic efficacy of the widely used antiarrhythmic, amiodarone, and diuretic, spironolactone, and combinations of them compared to PZQ. Mice were infected by Schistosoma mansoni "S. mansoni" cercariae (Egyptian strain), then they were divided into two major groups: Early- [3 weeks post-infection (wpi)] and late- [6 wpi] treated. Each group was subdivided into seven subgroups: positive control, PZQ, amiodarone, spironolactone, PZQ combined with amiodarone, PZQ combined with spironolactone, and amiodarone combined with spironolactone-treated groups. Among the early-treated groups, spironolactone had the best therapeutic impact indicated by a 69.4% reduction of total worm burden (TWB), 38.6% and 48.4% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 49%. Whereas, among the late-treated groups, amiodarone combined with PZQ was superior to PZQ alone evidenced by 96.1% reduction of TWB with the total disappearance of female and copula in the liver and intestine, 53.1% and 84.9% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 67.6%. Comparatively, spironolactone was superior to PZQ and amiodarone in the early treatment phase targeting immature stages, while amiodarone had a more potent effect when combined with PZQ in the late treatment phase targeting mature schistosomes.


Subject(s)
Amiodarone , Disease Models, Animal , Praziquantel , Schistosoma mansoni , Schistosomiasis mansoni , Animals , Schistosomiasis mansoni/drug therapy , Schistosomiasis mansoni/parasitology , Mice , Schistosoma mansoni/drug effects , Praziquantel/therapeutic use , Praziquantel/pharmacology , Amiodarone/therapeutic use , Amiodarone/pharmacology , Female , Spironolactone/therapeutic use , Spironolactone/pharmacology , Schistosomicides/therapeutic use , Schistosomicides/pharmacology , Male , Anthelmintics/therapeutic use , Anthelmintics/pharmacology , Treatment Outcome , Drug Therapy, Combination , Liver/parasitology
11.
Vet Parasitol ; 329: 110200, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38744230

ABSTRACT

Histomonas meleagridis, an anaerobic intercellular parasite, is known to infect gallinaceous birds, particularly turkeys and chickens. The resurgence of histomonosis in recent times has resulted in significant financial setbacks due to the prohibition of drugs used for disease treatment. Currently, research on about H. meleagridis primarily concentrate on the examination of its virulence, gene expression analysis, and the innate immunity response of the host organism. However, there is a lack of research on differentially expressed miRNAs (DEMs) related to liver infection induced by H. meleagridis. In this study, the weight gain and pathological changes at various post-infection time points were evaluated through animal experiments to determine the peak and early stages of infection. Next, High-throughput sequencing was used to examine the expression profile of liver miRNA at 10 and 15 days post-infection (DPI) in chickens infected with the Chinese JSYZ-F strain of H. meleagridis. A comparison with uninfected controls revealed the presence of 120 and 118 DEMs in the liver of infected chickens at 10 DPI and 15 DPI, respectively, with 74 DEMs being shared between the two time points. Differentially expressed microRNAs (DEMs) were categorized into three groups based on the time post-infection. The first group (L1) includes 45 miRNAs that were differentially expressed only at 10 DPI and were predicted to target 1646 genes. The second group (L2) includes 43 miRNAs that were differentially expressed only at 15 DPI and were predicted to target 2257 genes. The third group (L3) includes 75 miRNAs that were differentially expressed at both 10 DPI and 15 DPI and were predicted to target 1623 genes. At L1, L2, and L3, there were 89, 87, and 41 significantly enriched Gene Ontology (GO) terms, respectively (p<0.05). The analysis of differentially expressed miRNA target genes using KEGG pathways revealed significant enrichment at L1, L2, and L3, with 3, 4, and 5 pathways identified, respectively (p<0.05). This article suggests that the expression of liver miRNA undergoes dynamic alterations due to H. meleagridis and the host. It showed that the expression pattern of L1 class DEMs was more conducive to regulating the development of the inflammatory response, while the L2 class DEMs were more conducive to augmenting the inflammatory response. The observed patterns of miRNA expression associated with inflammation were in line with the liver's inflammatory process following infection. The results of this study provide a basis for conducting a comprehensive analysis of the pathogenic mechanism of H. meleagridis from the perspective of host miRNAs.


Subject(s)
Chickens , Liver , MicroRNAs , Poultry Diseases , Trichomonadida , Animals , Chickens/parasitology , MicroRNAs/genetics , MicroRNAs/metabolism , Poultry Diseases/parasitology , Liver/parasitology , Liver/metabolism , Trichomonadida/genetics , Protozoan Infections, Animal/parasitology , Transcriptome , Gene Expression Profiling/veterinary
12.
ACS Infect Dis ; 10(6): 2101-2107, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38733389

ABSTRACT

The bioluminescent Leishmania infantum BALB/c mouse model was used to evaluate the parasiticidal drug action kinetics of the reference drugs miltefosine, paromomycin, sodium stibogluconate, and liposomal amphotericin B. Infected mice were treated for 5 days starting from 7 days post-infection, and parasite burdens were monitored over time via bioluminescence imaging (BLI). Using nonlinear regression analyses of the BLI signal, the parasite elimination half-life (t1/2) in the liver, bone marrow, and whole body was determined and compared for the different treatment regimens. Significant differences in parasiticidal kinetics were recorded. A single intravenous dose of 0.5 mg/kg liposomal amphotericin B was the fastest acting with a t1/2 of less than 1 day. Intraperitoneal injection of paromomycin at 320 mg/kg for 5 days proved to be the slowest with a t1/2 of about 5 days in the liver and 16 days in the bone marrow. To conclude, evaluation of the cidal kinetics of the different antileishmanial reference drugs revealed striking differences in their parasite elimination half-lives. This BLI approach also enables an in-depth pharmacodynamic comparison between novel drug leads and may constitute an essential tool for the design of potential drug combinations.


Subject(s)
Antiprotozoal Agents , Leishmania infantum , Leishmaniasis, Visceral , Luminescent Measurements , Mice, Inbred BALB C , Animals , Leishmania infantum/drug effects , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/pharmacokinetics , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/parasitology , Mice , Female , Liver/parasitology , Liver/drug effects , Bone Marrow/parasitology , Bone Marrow/drug effects , Kinetics , Disease Models, Animal
13.
Trends Parasitol ; 40(6): 446-448, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38772757

ABSTRACT

Liebold et al. recently revealed how the identity of dying cells drives distinct changes to the macrophages which engulf and clear them, a process known as efferocytosis. During infection with the helminth Schistosoma mansoni, liver macrophages recapitulate these phenotypes, mediated by Axl/MerTK receptors and regulating egg burdens.


Subject(s)
Macrophages , Phagocytosis , Schistosoma mansoni , Animals , Macrophages/immunology , Macrophages/parasitology , Schistosoma mansoni/physiology , Schistosoma mansoni/immunology , Schistosomiasis mansoni/immunology , Schistosomiasis mansoni/parasitology , Receptor Protein-Tyrosine Kinases/metabolism , Receptor Protein-Tyrosine Kinases/immunology , Humans , Liver/parasitology , Liver/immunology , Axl Receptor Tyrosine Kinase , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , c-Mer Tyrosine Kinase/metabolism , c-Mer Tyrosine Kinase/physiology , Efferocytosis
14.
Micron ; 183: 103658, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38788484

ABSTRACT

Schistosomiasis represents a serious public health problem, a disease for which the circulating cathodic antigen (CCA) is a relevant biomarker. Quantum dots (QDs) are advantageous fluorescent nanoparticles that can be used as specific nanoprobes. In this study, a nanotool based on QDs and anti-CCA antibodies was developed, which, in association with fluorescence microscopy, was applied to trace and evaluate the CCA profile in schistosomiasis-infected tissue samples. Kidney and liver tissues from mice at different disease phases were used as models. QDs and the conjugates were characterized by absorption and emission spectroscopies. Microscopy analyses were used to map and assess CCA accumulation in infected tissue slices in respect to non-infected control samples. The fluorescent microplate assay (FMA) and Zeta potential (ζ) analyses indicated an effective conjugation, which was corroborated by the absence of labeling in non-infected tissue slices (which lack CCA) after incubation with the nanoprobe. Infected liver and kidney tissues exhibited notable staining by the QDs-anti-CCA conjugate. The CCA accumulation increased as follows: 30 < 60 = 120 days post-infection, with 30, 60, and 120 days corresponding to the pre-patent, acute, and beginning of chronic disease phases, respectively. Therefore, this innovative approach, combining imaging acquisition with the sensitivity and specificity of the QDs-anti-CCA conjugate, demonstrated efficiency in locating and comparatively evaluating CCA deposition in biological samples, thereby opening new possibilities for schistosomiasis research.


Subject(s)
Antigens, Helminth , Kidney , Liver , Microscopy, Fluorescence , Quantum Dots , Animals , Antigens, Helminth/immunology , Antigens, Helminth/analysis , Mice , Liver/parasitology , Kidney/parasitology , Microscopy, Fluorescence/methods , Schistosomiasis/diagnosis , Schistosomiasis/parasitology , Female
15.
Parasitol Res ; 123(5): 200, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696061

ABSTRACT

The humpback whale (Megaptera novaeangliae) is a cosmopolitan migratory, seasonal mysticete that frequents the Brazilian coast. Strands of specimens may occur during the migratory stay in the country. In 2021 and 2022, three live humpback whales stranded on the coast of Rio Grande do Sul and Santa Catarina states in southern Brazil. After euthanasia, specimens were necropsied, and organs were thoroughly examined for lesions. Grossly, in all three cases, the liver exhibited multifocal, irregular, firm, white areas on the hepatic capsule, which extended into the parenchyma. On the cut surface, the livers were yellow to pale brown with orangish to greenish areas, the bile ducts were prominent, thickened, and severely dilated, and leaf-shaped flukes were found inside of them. Additionally, one case showed moderate atrophy of the right hepatic lobe. The histological findings included dilation of bile ducts, hyperplasia of the bile duct epithelium, marked inflammatory infiltration of lymphocytes, plasma cells, and eosinophils, and portal fibrosis. The parasite Brachycladium goliath was both morphologically and molecularly identified based on diagnostic key for trematodes and the original description of the species, and the amplification and sequencing of the ITS-2 region, respectively. Even though hepatic injury was not the primary cause of stranding, it may have contributed to the debilitation of the whales. To the authors' knowledge, this is the first study that reports M. novaeangliae as a definitive host of B. goliath and that describes the lesions caused by the parasite in cetaceans.


Subject(s)
Humpback Whale , Liver , Trematoda , Trematode Infections , Animals , Humpback Whale/parasitology , Brazil , Trematoda/classification , Trematoda/anatomy & histology , Trematoda/isolation & purification , Trematoda/genetics , Liver/parasitology , Liver/pathology , Trematode Infections/veterinary , Trematode Infections/parasitology , Phylogeny , Male
16.
Vet Immunol Immunopathol ; 273: 110775, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38776648

ABSTRACT

BACKGROUND: Hydatid disease is caused by the larval stages of the canine tapeworm Echinococcus granulosus. It is one of the most critical helminthic diseases, representing worldwide public health and socio-economic concern. AIM: This study aimed to investigate the expression of apoptosis and immune response within hepatic tissues of humans and sheep infected with the Hydatid cyst. METHODS: Paraffin-embedded tissue was prepared from each tissue sample and used for histopathological examination by Haematoxylin- Eosin. Also, toluidine blue staining was used for mast cell detection, while an immunohistochemical study was performed to assess CD3 T lymphocytes, CD4 helper T lymphocytes, CD8 cytotoxic T lymphocytes, CD20 memory B lymphocytes, CD68 macrophage, and caspase-3 antibodies. RESULTS: The histological examination revealed significant changes, including the infiltration of inflammatory cells, predominantly lymphocytes with scattered giant cells, necrotic hepatic tissue, and fibrosis. Toluidine blue stain revealed a higher number of mast cells (5 cells/field) in humans compared to sheep (3.6 cells/field). The immunohistochemical analysis confirmed that the CD3 were the most predominant inflammatory cell in the hepatic tissue of humans (intensive 70%), and sheep (moderate 38.47%). Caspase-3 was observed in all samples in different grades and mostly in human liver tissue. CONCLUSION: This data could aid in recognizing immunological markers for differentiating disease progression, as well as enhance the understanding of local immune responses to cystic Echinococcosis (CE). The findings could provide preliminary data for future studies on immune responses associated with Hydatid cysts.


Subject(s)
Echinococcosis, Hepatic , Sheep Diseases , Animals , Sheep/immunology , Echinococcosis, Hepatic/immunology , Echinococcosis, Hepatic/veterinary , Echinococcosis, Hepatic/parasitology , Sheep Diseases/immunology , Sheep Diseases/parasitology , Humans , Liver/parasitology , Liver/immunology , Liver/pathology , Male , Female , Echinococcosis/immunology , Echinococcosis/veterinary , Echinococcus granulosus/immunology , Apoptosis/immunology , Caspase 3/immunology , Adult
17.
PLoS Pathog ; 20(5): e1012268, 2024 May.
Article in English | MEDLINE | ID: mdl-38814989

ABSTRACT

The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. After laying, the egg "winners" attach to the endothelium of the mesenteric vein and, after a period of development, induce the growth of a small granuloma, which facilitates their passage to the intestinal lumen. Egg "losers" carried by the bloodstream to non-specific tissues also undergo full development and induce large granuloma formation, but their life ends there. Although these trapped eggs represent a dead end in the parasite life cycle, the vast majority of studies attempting to describe the biology of the S. mansoni eggs have studied these liver-trapped "losers" instead of migrating intestinal "winners". This raises the fundamental question of how these eggs differ. With robust comparative transcriptomic analysis performed on S. mansoni eggs isolated 7 weeks post infection, we show that gene expression is critically dependent on tissue localization, both in the early and late stages of development. While mitochondrial genes and venom allergen-like proteins are significantly upregulated in mature intestinal eggs, well-described egg immunomodulators IPSE/alpha-1 and omega-1, together with micro-exon genes, are predominantly expressed in liver eggs. In addition, several proteases and protease inhibitors previously implicated in egg-host interactions display clear tissue-specific gene expression patterns. These major differences in gene expression could be then reflected in the observed different ability of liver and intestinal soluble egg antigens to elicit host immune responses and in the shorter viability of miracidia hatched from liver eggs. Our comparative analysis provides a new perspective on the biology of parasite's eggs in the context of their development and tissue localization. These findings could contribute to a broader and more accurate understanding of parasite eggs interactions with the host, which have historically been often restricted to liver eggs and sometimes inaccurately generalized.


Subject(s)
Liver , Schistosoma mansoni , Schistosomiasis mansoni , Animals , Schistosoma mansoni/immunology , Schistosoma mansoni/genetics , Liver/parasitology , Liver/immunology , Liver/metabolism , Schistosomiasis mansoni/immunology , Schistosomiasis mansoni/parasitology , Mice , Ovum/metabolism , Ovum/immunology , Intestines/parasitology , Intestines/immunology , Antigens, Helminth/immunology , Helminth Proteins/genetics , Helminth Proteins/metabolism , Helminth Proteins/immunology , Female , Egg Proteins
18.
Immun Inflamm Dis ; 12(4): e1236, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38652009

ABSTRACT

OBJECTIVE: To explore the role of miRNA in liver damage caused by Echinococcus multilocularis infection. METHODS: Six female C57BL mice were randomly divided into two groups, the control group and the infection group. Mice in the control group were injected with 100 µL PBS through the hepatic portal vein, and mice in the infection group were infected with E. multilocularis via the hepatic portal vein to establish a mouse model of infection. Small RNA sequencing was performed for detecting the expression of miRNAs in the liver of mice infected with 2000 E. multilocularis after 3 months of infection, screen out miRNAs related to liver damage, and verify by RT-PCR. RESULTS: Seventy-one differentially expressed miRNAs were found in the liver in comparison with control, and a total of 36 mouse miRNAs with |FC| >0.585 were screened out, respectively. In addition, Targetscan (V5.0) and miRanda (v3.3a) software were used to predict differential miRNAs target genes and functional enrichment of target genes. Functional annotation showed that "cytokine-cytokine interaction," "positive regulation of cytokine production," "inflammatory response," and "leukocyte activation" were enriched in the liver of E. multilocularis-infected mice. Moreover, the pathways "human cytomegalovirus infection," "cysteine and methionine metabolism," "Notch signaling pathway," and "ferroptosis" were involved in liver disease. Furthermore, four miRNAs (mmu-miR-30e-3p, mmu-miR-203-3p, mmu-miR-125b-5p, and mmu-miR-30c-2-3p) related to liver injury were screened and verified. CONCLUSION: This study revealed that the expression profiling of miRNAs in the livers was changed after E. multilocularis infection, and improved our understanding of the transcriptomic landscape of hepatic echinococcosis in mice.


Subject(s)
Echinococcus multilocularis , Liver , Mice, Inbred C57BL , MicroRNAs , Portal Vein , Animals , MicroRNAs/genetics , Mice , Female , Portal Vein/pathology , Portal Vein/parasitology , Echinococcus multilocularis/genetics , Liver/parasitology , Liver/metabolism , Liver/pathology , Disease Models, Animal , Gene Expression Profiling , Echinococcosis/pathology
19.
Vet Res ; 55(1): 53, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658996

ABSTRACT

Gene expression for Th1/Th2 cytokines (IL-4 and IFN-É£), regulatory cytokines (TGF-ß and IL-10) and the transcriptional factor FoxP3 was analyzed in the liver and hepatic lymph nodes (HLN) from sheep immunized with partially protective and non-protective vaccine candidates and challenged with Fasciola hepatica. FoxP3 T cells were also evaluated by immunohistochemistry (IHQ). The most remarkable difference between the partially protected vaccinated (V1) group and the non-protected vaccinated (V2) group was a more severe expansion of FoxP3 T cells recorded by IHQ in both the liver and HLN of the V2 group as compared to the V1 group, whereas no differences were found between the V2 group and the infected control (IC) group. Similar results were recorded for FoxP3 gene expression although significant differences among V1 and V2 groups were only significant in the HLN, while FoxP3 gene expression was very similar in the V2 and IC groups both in the liver and HLN. No significant differences for the remaining cytokines were recorded between the V1 and V2 groups, but in the liver the V2 group shows significant increases of IFN-É£ and IL-10 as compared to the uninfected control (UC) group whereas the V1 group did not. The lower expansion of FoxP3 T cells and lower increase of IFN-É£ and IL-10 in the partially protected vaccinated group may be related with lower hepatic lesions and fluke burdens recorded in this group as compared to the other two infected groups. The most relevant change in regulatory cytokine gene expression was the significant increase of TGF-ß in the liver of IC, V1 and V2 groups as compared to the UC group, which could be related to hepatic lesions.


Subject(s)
Cytokines , Fasciola hepatica , Fascioliasis , Forkhead Transcription Factors , Sheep Diseases , Animals , Fascioliasis/veterinary , Fascioliasis/prevention & control , Fascioliasis/immunology , Fasciola hepatica/immunology , Sheep , Forkhead Transcription Factors/metabolism , Sheep Diseases/prevention & control , Sheep Diseases/immunology , Sheep Diseases/parasitology , Cytokines/metabolism , Liver/parasitology , Liver/immunology , Vaccines/immunology , Vaccines/administration & dosage , Th1 Cells/immunology , Lymph Nodes/immunology , Female , Th2 Cells/immunology
20.
Anal Chem ; 96(16): 6311-6320, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38594017

ABSTRACT

Schistosomiasis is a neglected tropical disease caused by worm parasites of the genus Schistosoma. Upon infection, parasite eggs can lodge inside of host organs like the liver. This leads to granuloma formation, which is the main cause of the pathology of schistosomiasis. To better understand the different levels of host-pathogen interaction and pathology, our study focused on the characterization of glycosphingolipids (GSLs). For this purpose, GSLs in livers of infected and noninfected hamsters were studied by combining high-spatial-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) with nanoscale hydrophilic interaction liquid chromatography tandem mass spectrometry (nano-HILIC MS/MS). Nano-HILIC MS/MS revealed 60 GSL species with a distinct saccharide and ceramide composition. AP-SMALDI MSI measurements were conducted in positive- and negative-ion mode for the visualization of neutral and acidic GSLs. Based on nano-HILIC MS/MS results, we discovered no downregulated but 50 significantly upregulated GSLs in liver samples of infected hamsters. AP-SMALDI MSI showed that 44 of these GSL species were associated with the granulomas in the liver tissue. Our findings suggest an important role of GSLs during granuloma formation.


Subject(s)
Glycosphingolipids , Liver , Schistosoma mansoni , Schistosomiasis mansoni , Animals , Glycosphingolipids/metabolism , Glycosphingolipids/chemistry , Liver/metabolism , Liver/parasitology , Cricetinae , Schistosomiasis mansoni/parasitology , Schistosomiasis mansoni/metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tandem Mass Spectrometry , Mesocricetus , Chromatography, Liquid , Male
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