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1.
Front Biosci (Landmark Ed) ; 29(3): 124, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38538283

ABSTRACT

BACKGROUND: Toxocara canis (T. canis) is a helminth parasite of zoonotic and veterinary health significance that causes the disease known as Toxocariasis. This disease has been associated with conditions of poverty, especially in tropical climate zones throughout the world. Although it rarely causes important clinical manifestations, T. canis can lead to blindness, meningoencephalitis, or other nervous manifestations in humans. Moreover, some studies show its importance in the development of tumor growth, which have been associated with the parasite's ability to modulate the host's immune response. While different studies have evaluated the immune response during this disease, currently, there are no studies where the infection is analyzed from the perspective of sexual dimorphism. METHODS: To evaluate sex differences in susceptibility, we analyzed lesions and parasite loads in lung and liver at 7 days post-infection. In addition, immune cell subpopulations were analyzed in spleen, mesenteric and peripheral lymph nodes. Finally, the production of cytokines and specific antibodies were determined in the serum. Statical analyses were performed using a Two-way ANOVA and a post-hoc Bonferroni multiple comparison test. RESULTS: Female rats had a higher number of larvae in the liver, while male rats had them in the lungs. The percentages of immune cells were evaluated, and in most cases, no significant differences were observed. Regarding the cytokines production, infection can generate a decrease in Th1 such as IL-1ß in both sexes and IL-6 only in females. In the case of Th2, IL-4 increases only in infected males and IL-5 increases in males while decreasing in females due to the effect of infection. IL-10 also decreases in both sexes as a consequence of the infection, and TGF-ß only in females. Finally, the infection generates the production of antibodies against the parasite, however, their quantity is lower in females. CONCLUSIONS: This study demonstrates that T. canis infection is dimorphic and affects females more than males. This is due to a polarization of the inadequate immune response, which is reflected as a higher parasite load in this sex.


Subject(s)
Toxocara canis , Toxocariasis , Humans , Female , Rats , Male , Animals , Toxocariasis/parasitology , Toxocariasis/pathology , Toxocara canis/physiology , Sex Characteristics , Cytokines , Immunity
2.
Parasitol Res ; 122(6): 1327-1332, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37046027

ABSTRACT

Toxocara tanuki is a common large roundworm in raccoon dogs. Experimental infection studies of T. tanuki in mice were conducted to clarify the distribution and infectivity of larvae in tissue. Groups of BALB/c and C57BL/6 mice (n = 5 mice/group) were each inoculated with 1000 embryonated T. tanuki eggs and necropsied at 7, 31, 91, and 182 days post inoculation (dpi). The number of larvae in the central nervous system, heart, lungs, kidneys, spleen, gastrointestinal tract, liver, and carcass was examined. Larvae obtained from the aforementioned mice on different days of the necropsy were orally inoculated into four groups of ICR mice (n = 6 mice/group) that were then necropsied at 21 dpi. Larvae were recovered from all mice. In the BALB/c and C57BL/6 mice, most of the larvae (> 88.7%) were recovered from the liver and the remainder from other tissues. The total number of larvae recovered from C57BL/6 mice was significantly higher than that from BALB/c mice, but no difference in the relative larval distribution within the viscera between the two mouse strains was observed. The mean recovery percentage of larvae from ICR mice infected with 182-day-old tissue larvae was 3.3%. Our findings showed that T. tanuki larvae migrated predominantly to the liver of mice and that the larvae maintained their infectivity for at least half a year.


Subject(s)
Toxocara canis , Toxocariasis , Animals , Mice , Toxocara , Larva/physiology , Mice, Inbred ICR , Mice, Inbred C57BL , Lung , Liver , Toxocara canis/physiology
3.
Front Cell Infect Microbiol ; 12: 890589, 2022.
Article in English | MEDLINE | ID: mdl-36176575

ABSTRACT

A global lipidomic analysis using liquid chromatography-tandem mass spectrometry was performed on the liver of beagle dogs infected with Toxocara canis to profile hepatic lipid species at 12 h post-infection (hpi), 24 hpi, and 36 days post-infection (dpi). This analysis identified six categories and 42 subclasses of lipids, including 173, 64, and 116 differentially abundant lipid species at 12 hpi, 24 hpi, and 36 dpi, respectively. Many of the identified lysophospholipids, such as lysophosphatidylglycerol, lysophosphatidylserine, and lysophosphatidylcholine, may contribute to the migration and development of T. canis during the early infection stage. Pathway analysis revealed significant alterations of several immune-inflammatory pathways, such as the B-cell receptor signaling pathway, the NF-kappa B signaling pathway, and the C-type lectin receptor signaling pathway at 12 and 24 hpi. These findings demonstrate the value of lipidomic profiling in revealing the extent of changes in the composition and abundance of hepatic lipidome caused by T. canis infection and their relevance to the pathophysiology of toxocariasis in beagle dogs.


Subject(s)
Dog Diseases , Toxocara canis , Toxocariasis , Animals , Dogs , Lectins, C-Type , Lipidomics , Liver , Lysophosphatidylcholines , NF-kappa B , Receptors, Antigen, B-Cell , Toxocara canis/physiology
4.
Article in English | MEDLINE | ID: mdl-33533812

ABSTRACT

Human toxocariasis consists of chronic tissue parasitosis that is difficult to treat and control. This study aimed to evaluate the action of the probiotic Lactobacillus acidophilus ATCC 4356 on larvae of Toxocara canis and the effect of IFN-γ cytokine on parasite-host in vivo (1.109 CFU) and in vitro (1.106, 1.107, 1.108, 1.109 CFU) interactions. Four groups of six BALB/c mice were formed: G1 - L. acidophilus supplementation and T. canis infection; G2 - T. canis infection; G3 - L. acidophilus supplementation; and G4 - PBS administration. Mice were intragastrically suplemented with probiotics for 15 days before inoculation and 48 h after inoculation with 100 T. canis eggs. The inoculation of T. canis was also perfomed intragastrically. The recovery of larvae took place through digestion of liver and lung tissues; the evaluation of IFN-γ gene transcription in leukocytes was performed by qPCR. The in vitro test consisted of incubating the probiotic with T. canis larvae. The supplementation of probiotics produced a reduction of 57.7% (p = 0.025) in the intensity of infection of T. canis larvae in mice, whereas in the in vitro test, there was no larvicidal effect. In addition, a decrease in the IFN-γ gene transcription was observed in both, T. canis-infected and uninfected mice, regardless of whether or not they received supplementation. The probiotic L. acidophilus ATCC 4356 reduced T. canis infection intensity in mice, however, the probiotic did not have a direct effect on larvae, demonstrating the need of interaction with the host for the beneficial effect of the probiotic to occur. Yet, the proinflammatory cytokine IFN-γ did not apparently contributed to the observed beneficial effect of probiotics.


Subject(s)
Lactobacillus acidophilus/drug effects , Probiotics/administration & dosage , Toxocara canis/drug effects , Toxocariasis/drug therapy , Toxocariasis/prevention & control , Animals , Lactobacillus , Larva/drug effects , Mice , Mice, Inbred BALB C , Probiotics/pharmacology , Toxocara canis/microbiology , Toxocara canis/physiology , Toxocariasis/parasitology
5.
Pan Afr Med J ; 36: 150, 2020.
Article in English | MEDLINE | ID: mdl-32874414

ABSTRACT

Hepatic toxocarosis is caused by the dog´s roundworm, Toxocara canis. Responsible for an eosinophilic inflammatory syndrome causing liver damage that can be detected on ultrasound, computed tomography and sometimes magnetic resonance imaging. We report the case of a nine-year-old child, living in countryside, with a notion of cohabitation with canids. He presented a digestive symptomatology revealed by abdominal pain, with a hemeosinophilia in the hemogram. The etiological assessment of hyper eosinophilia objectified a positive Toxocara canisserology. The imaging assessment in search of digestive visceral lesions, found multiple heterogeneous hypoechogenic areas, poorly defined, scattered in the liver. On the abdominal CT scan, its areas appear of unenhanced density and low density and better visible after injection of contrast product. This observation reveals that imagery, although not very specific, helps in the assessment of liver damage from digestive toxocarosis.


Subject(s)
Larva Migrans, Visceral/diagnosis , Toxocara canis/physiology , Albendazole/therapeutic use , Animals , Child , Humans , Larva Migrans, Visceral/drug therapy , Liver Diseases, Parasitic/diagnosis , Liver Diseases, Parasitic/drug therapy , Magnetic Resonance Imaging , Male , Tomography, X-Ray Computed , Ultrasonography
6.
Adv Parasitol ; 109: 17-38, 2020.
Article in English | MEDLINE | ID: mdl-32381197

ABSTRACT

This review covers the systematics and nomenclature of the Ascaridoid genus toxocara, and more specifically the species Toxocara canis and Toxocara cati. Also discussed is the discovery of the persistence of these larvae in the tissues of paratenic hosts, and the role that other species of this genus might or could play in other such hosts; including those where the life cycle has been described, i.e., Toxocara vitulorum, Toxocara pteropodis, Toxocara mackerrasae, and Toxocara tanuki. Also examined is the work that led to the realization that the larval stage leaving the egg actually being a third rather than a second stage larva. Also discussed on the work showing that the larvae can persist in paratenic host with remarkable longevity without undergoing any morphological change for years and that these larvae can be transmitted from one paratenic host to another by ingestion. People are usually infected by the ingestion of eggs containing third-stage larvae, but infections also occur on occasions from the ingestion of uncooked paratenic hosts.


Subject(s)
Larva Migrans/parasitology , Toxocara/physiology , Toxocariasis/parasitology , Animals , History, 20th Century , Humans , Larva , Larva Migrans/history , Toxocara/classification , Toxocara canis/physiology , Toxocariasis/history
7.
Adv Parasitol ; 109: 39-61, 2020.
Article in English | MEDLINE | ID: mdl-32381209

ABSTRACT

This review describes the morphology and ultrastructure of the third-stage larva of Toxocara canis, the larval stage that hatches from the egg and persists in the tissues of various paratenic hosts including infected humans. This larva remains unchanged as it passes from host to host and lives for extended periods in this same body form until it makes its way to the gastro-intestinal tract of its final host. There has been less work on the anatomy and ultrastructure of the larva of Toxocara cati, but overall, it appears very similar to that of T. canis with the only apparent difference being that the larva is a few microns thinner in diameter. The paper describes the anatomy and ultrastructure of the larva and the various major structures of the various body systems including the cuticle, hypodermis, the nervous tissue, oesophagus and the lumen-free intestine, and the large excretory gland cell that fills much of the pseudocoel and which appears to be the source of the components that are recognized immunologically by the infected host. It is suggested that further detailed studies on the larva could provide significant information that would allow a greater understanding of how the larva persists within these hosts and may provide information that would make the larva an excellent link to work on nematode anatomy that would link the work being done with this model system to that of Caenorhabditis elegans and the large amount of historical work already performed on adult ascaridoid nematodes.


Subject(s)
Toxocara canis/anatomy & histology , Toxocara/anatomy & histology , Animals , Humans , Larva , Toxocara/physiology , Toxocara canis/physiology
8.
Adv Parasitol ; 109: 641-653, 2020.
Article in English | MEDLINE | ID: mdl-32381222

ABSTRACT

Toxocara spp. (T. canis and T. cati) are the dominant ascarids of domestic dogs and cats, respectively, in populated regions of southern Canada, where they pose animal and public health concerns. A review of the published literature indicated that prevalence of both parasites is declining in more recent studies (post 2000), likely due to changes in animal husbandry as well as use of anthelmintics. Geographically, prevalence was higher in the east (Atlantic), and in more southerly locations, possibly due to more favourable climate conditions for egg survival and development. At northern latitudes and in wild felids and canids in general, the non-zoonotic ascarid Toxascaris leonina appears to outcompete Toxocara spp.; however, T. leonina is rare in domestic cats in Canada. Prevalence of Toxocara spp. was higher in cats than dogs, shelter/rural/remote/feral/stray vs owned animals, and young vs adult animals, as has been observed in many other studies and regions of the world. While the regional prevalences in this review should be interpreted carefully in light of variation in diagnostic methods and study populations, they generally follow the same trends observed in a recent national study of shelter animals. This review is a timely summary of the state of the published knowledge on prevalence of Toxocara spp. in Canada, and highlights knowledge gaps to be addressed, including the northern distributional limits of these species in Canada, the potential for transmission to and from wildlife hosts, and the public health significance of the parasite in the mainstream Canadian population.


Subject(s)
Cat Diseases/epidemiology , Dog Diseases/epidemiology , Toxocara , Toxocariasis/epidemiology , Animals , Canada/epidemiology , Cat Diseases/parasitology , Cats , Dog Diseases/parasitology , Dogs , Prevalence , Toxocara/physiology , Toxocara canis/physiology , Toxocariasis/parasitology
9.
Parasite Immunol ; 42(11): e12760, 2020 11.
Article in English | MEDLINE | ID: mdl-32472559

ABSTRACT

Helminthic infection and the parallel host immune reactions are the results of a protracted dynamic co-interaction between the host and worms. An assessment of the effect of Toxocara canis infection on arthritis in rats stimulated by Freund's complete adjuvant (FCA) was the main purpose of the investigation. An arthritis model was established by the administration of 0.1 mL FCA in the palmar surface. Cytokine assessment, evaluating oedema and the use of a rheumatoid arthritis (RA) score provided evidence of the protective effects of T canis against adjuvant-induced arthritis (AIA). The cytokines TGF-ß, IFN-É£, IL-10 and IL-17 were measured to assess the anti-inflammatory effect of T canis infection. Besides, arthritis swelling findings were evaluated in rat paws. The data showed that T canis infection significantly modulated the immune response by alleviating inflammatory cytokines and increasing TGF-ß as an anti-inflammatory cytokine. Evaluations of arthritis swelling showed low severity and faster recuperation. These findings suggest that the products derived from T canis eggs might be a potential therapeutic candidate to treat autoimmune diseases like the arthritis.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Arthritis, Experimental/prevention & control , Freund's Adjuvant/adverse effects , Inflammation/prevention & control , Toxocara canis/physiology , Transforming Growth Factor beta/blood , Animals , Arthritis, Experimental/chemically induced , Cytokines/blood , Female , Injections, Intradermal , Joints/pathology , Larva , Male , Random Allocation , Rats , Rats, Wistar
10.
Parasit Vectors ; 13(1): 71, 2020 Mar 01.
Article in English | MEDLINE | ID: mdl-32113482

ABSTRACT

BACKGROUND: Ascarid infections are among the most prevalent intestinal parasitic infections occurring in dogs around the world, with Toxocara canis and Toxascaris leonina commonly observed. Toxocara canis can cause considerable disease in dogs and humans, and year-round prophylactic treatment and control in dogs is recommended. Elimination of immature stages of these parasites before egg-laying will reduce environmental contamination and the risk of infection for both dogs and humans. Studies were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced immature adult (L5) and adult T. canis, and adult T. leonina infections in dogs. METHODS: Six negative-controlled, masked, randomized laboratory studies were conducted. Two studies each evaluated efficacy against immature adult (L5) T. canis, adult T. canis, and adult T. leonina. Sixteen to 40 dogs were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy was based on the number of worms recovered at necropsy 7-10 days after treatment compared to placebo control. RESULTS: Based on geometric mean worm counts, efficacy of the sarolaner + moxidectin + pyrantel combination was ≥ 95.2% against immature adult T. canis, ≥ 97.3% against adult T. canis, and ≥ 89.7% against adult T. leonina. There were no treatment-related adverse events in any study. CONCLUSIONS: These studies confirm the efficacy of a single dose of a new oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against immature adult and adult T. canis, and adult T. leonina infections in dogs.


Subject(s)
Antinematodal Agents/administration & dosage , Ascaridida Infections/veterinary , Dog Diseases/drug therapy , Intestinal Diseases, Parasitic/veterinary , Administration, Oral , Animals , Ascaridida Infections/drug therapy , Azetidines/administration & dosage , Dogs , Drug Combinations , Female , Intestinal Diseases, Parasitic/drug therapy , Macrolides/administration & dosage , Male , Parasite Egg Count , Pyrantel/administration & dosage , Spiro Compounds/administration & dosage , Tablets , Toxascaris/drug effects , Toxascaris/physiology , Toxocara canis/drug effects , Toxocara canis/physiology , Treatment Outcome
11.
Parasitol Res ; 119(3): 1161-1165, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31848743

ABSTRACT

Probiotics have shown promising results as a potential method to control toxocariasis in mice inoculated with embryonated eggs of Toxocara canis. This study aimed to evaluate the protective effect of Saccharomyces boulardii in mice fed in natura chicken livers infected with T. canis. Twenty 15-day-old male Sussex chickens were inoculated with 300 T. canis embryonated eggs via intragastric catheter (GI). After 72 h of infection, each liver was collected and individually offered to a group of 20 mice. Mice that received supplemented ration with S. boulardii (1.107 colony forming units) and consumed in natura chicken liver showed reduction in infection intensity of 67.1%. This study demonstrated that administration of S. boulardii has potential as a probiotic to assist in controlling visceral toxocariasis caused by the consumption of viscera from paratenic hosts containing infective parasite larvae.


Subject(s)
Probiotics , Saccharomyces boulardii/physiology , Toxocariasis/microbiology , Toxocariasis/parasitology , Animals , Chickens/microbiology , Chickens/parasitology , Larva/drug effects , Liver/parasitology , Male , Mice , Toxocara canis/physiology
12.
PLoS Negl Trop Dis ; 13(9): e0007706, 2019 09.
Article in English | MEDLINE | ID: mdl-31557153

ABSTRACT

BACKGROUND: Somatic migration of Toxocara canis- and T. cati-larvae in humans may cause neurotoxocarosis (NT) when larvae accumulate and persist in the central nervous system (CNS). Host- or parasite-induced immunoregulatory processes contribute to the pathogenesis; however, detailed data on involvement of bioactive lipid mediators, e.g. oxylipins or eico-/docosanoids, which are involved in the complex molecular signalling network during infection and inflammation, are lacking. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate if T. canis- and T. cati-induced NT affects the homeostasis of oxylipins during the course of infection, a comprehensive lipidomic profiling in brains (cerebra and cerebella) of experimentally infected C57BL/6J mice was conducted at six different time points post infection (pi) by liquid-chromatography coupled to electrospray tandem mass spectrometry (LC-ESI-MS/MS). Only minor changes were detected regarding pro-inflammatory prostaglandins (cyclooxygenase pathway). In contrast, a significant increase of metabolites resulting from lipoxygenase pathways was observed for both infection groups and brain regions, implicating a predominantly anti-inflammatory driven immune response. This observation was supported by a significantly increased 13-hydroxyoctadecadienoic acid (HODE)/9-HODE ratio during the subacute phase of infection, indicating an anti-inflammatory response to neuroinfection. Except for the specialised pro-resolving mediator (SPM) neuroprotectin D1 (NPD1), which was detected in mice infected with both pathogens during the subacute phase of infection, no other SPMs were detected. CONCLUSIONS/SIGNIFICANCE: The obtained results demonstrate the influence of Toxocara spp. on oxylipins as part of the immune response of the paratenic hosts. Furthermore, this study shows differences in the alteration of the oxylipin composition between T. canis- and T. cati-brain infection. Results contribute to a further understanding of the largely unknown pathogenesis and mechanisms of host-parasite interactions during NT.


Subject(s)
Brain Diseases/parasitology , Oxylipins/chemistry , Toxocara canis/physiology , Toxocariasis/immunology , Toxocariasis/parasitology , Animals , Brain/immunology , Brain Chemistry , Brain Diseases/immunology , Docosahexaenoic Acids/immunology , Female , Humans , Inflammation Mediators/chemistry , Inflammation Mediators/immunology , Larva/physiology , Mice , Mice, Inbred C57BL , Oxylipins/immunology
13.
Parasitol Res ; 118(9): 2591-2600, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31350619

ABSTRACT

Infective larvae of Toxocara canis and T. cati, the common roundworms of dogs and cats, may invade the central nervous system of paratenic hosts, including humans, causing neurotoxocarosis (NT). Previous studies on NT in the model organism "mouse" have indicated distinct differences between T. canis and T. cati regarding larval migration patterns as well as the severity of clinical symptoms and behavioural alterations. The objective of the present study was to provide an extensive characterization of the underlying histopathological alterations, comparing T. canis- and T. cati-induced changes in different brain areas over the course of murine infection. Four histological sections of five brains each of T. canis- and T. cati-infected as well as uninfected C57Bl/6 mice were investigated 7, 14, 28, 42, 70 and 98 days post infection (dpi), while brains of T. cati-infected and control mice were also available 120 and 150 dpi. In addition to haematoxylin-eosin and luxol fast blue-cresyl violet staining, immunohistochemistry was employed to study microglia/macrophage cell morphology and to detect accumulation of ß-amyloid precursor protein (ß-APP) as an indicator of axonal damage. Haemorrhages, eosinophilic vasculitis and activated microglia/macrophages were detected in both infection groups starting 7 dpi, followed by eosinophilic meningitis in cerebra as from 14 dpi. Overall, little differences in the proportion of animals affected by these alterations were found between the two infection groups. In contrast, the proportion of animals displaying ß-APP accumulation was significantly higher in the T. canis than T. cati group as from 28 dpi regarding the cerebrum as well as at 98 dpi regarding the cerebellum. In T. canis-infected mice, myelinophagic microglia/macrophages ("gitter cells") appeared as from 14 dpi, whereas these were first observed at 70 dpi in T. cati-infected animals. The proportion of animals displaying demyelination and/or gitter cells in the cerebrum was significantly higher in the T. canis than T. cati group as from 28 dpi, and at 28 and 42 dpi regarding the cerebellum. Earlier and more severe neurodegeneration during T. canis- than T. cati-induced NT, especially in the cerebrum, may explain the differences in behavioural alterations observed in previous studies. In addition to differences in larval migration preferences, immunological processes may contribute to these patterns, which warrant further investigation.


Subject(s)
Toxocara canis/physiology , Toxocariasis/parasitology , Toxoplasmosis, Cerebral/parasitology , Amyloid beta-Peptides/metabolism , Animals , Brain/metabolism , Brain/parasitology , Brain/pathology , Disease Models, Animal , Female , Humans , Larva/physiology , Male , Mice , Mice, Inbred C57BL , Toxocara canis/immunology , Toxocariasis/metabolism , Toxocariasis/pathology , Toxoplasmosis, Cerebral/metabolism , Toxoplasmosis, Cerebral/pathology
14.
Parasit Vectors ; 12(1): 32, 2019 Jan 14.
Article in English | MEDLINE | ID: mdl-30642380

ABSTRACT

BACKGROUND: Toxocara canis is quite closely related to Ascaris suum but its biology is more complex, involving a phase of arrested development (diapause or hypobiosis) in tissues as well as transplacental and transmammary transmission routes. In the present study, we explored and compared dauer-like signalling pathways of T. canis and A. suum to infer which components in these pathways might associate with, or regulate, this added complexity in T. canis. METHODS: Guided by information for Caenorhabditis elegans, we bioinformatically inferred and compared components of dauer-like signalling pathways in T. canis and A. suum using genomic and transcriptomic data sets. In these two ascaridoids, we also explored endogenous dafachronic acids (DAs), which are known to be critical in regulating larval developmental processes in C. elegans and other nematodes, by liquid chromatography-mass spectrometry (LC-MS). RESULTS: Orthologues of C. elegans dauer signalling genes were identified in T. canis (n = 55) and A. suum (n = 51), inferring the presence of a dauer-like signalling pathway in both species. Comparisons showed clear differences between C. elegans and these ascaridoids as well as between T. canis and A. suum, particularly in the transforming growth factor-ß (TGF-ß) and insulin-like signalling pathways. Specifically, in both A. suum and T. canis, there was a paucity of genes encoding SMAD transcription factor-related protein (daf-3, daf-5, daf-8 and daf-14) and insulin/insulin-like peptide (daf-28, ins-4, ins-6 and ins-7) homologues, suggesting an evolution and adaptation of the signalling pathway in these parasites. In T. canis, there were more orthologues coding for homologues of antagonist insulin-like peptides (Tc-ins-1 and Tc-ins-18), an insulin receptor substrate (Tc-ist-1) and a serine/threonine kinase (Tc-akt-1) than in A. suum, suggesting potentiated functional roles for these molecules in regulating larval diapause and reactivation. A relatively conserved machinery was proposed for DA synthesis in the two ascaridoids, and endogenous Δ4- and Δ7-DAs were detected in them by LC-MS analysis. Differential transcription analysis between T. canis and A. suum suggests that ins-17 and ins-18 homologues are specifically involved in regulating development and migration in T. canis larvae in host tissues. CONCLUSION: The findings of this study provide a basis for functional explorations of insulin-like peptides, signalling hormones (i.e. DAs) and related nuclear receptors, proposed to link to development and/or parasite-host interactions in T. canis. Elucidating the functional roles of these molecules might contribute to the discovery of novel anthelmintic targets in ascaridoids.


Subject(s)
Computational Biology , Mammals/parasitology , Signal Transduction/physiology , Toxocara canis/physiology , Amino Acid Sequence , Animals , Ascaris suum/physiology , Caenorhabditis elegans , Conserved Sequence , Gene Expression Regulation , Helminth Proteins/genetics , Helminth Proteins/metabolism , Host-Parasite Interactions , Models, Biological , Toxocara canis/genetics
15.
Exp Parasitol ; 198: 1-6, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30633913

ABSTRACT

The in vitro effect of progesterone in T. canis larvae on their enlargement and motility were evaluated, together to the possible presence of progesterone receptors (PRs). T. canis larvae were cultured in RPMI-1640 with different concentrations of progesterone (0, 20, 40, 80, 400 and 800 ng/mL). Enlargement and increases in motility were dependent on the concentration only from 0 to 80 ng/mL (p < 0.05). The mean percentage of PR + cells in newly obtained larvae as measured by flow cytometry was 8.16 ± 0.4. The number of PR + cells increased depending on concentration from 0 to 80 ng/mL (p < 0.001). Cells obtained from larvae stimulated at any of the studied hormone concentrations showed greater mean fluorescence intensity when compared to non-stimulated cells. Additionally, the expression and location of PR + cells were determined in the larvae. The sequence of an amplicon (420-bp) obtained by PCR from T. canis larvae showed 100% homology with a gene fragment that codes for the PR of the dog. PR + cells were immunolocated using confocal microscopy in the intestinal region of the larvae that had been recently obtained. The results of this study show that T. canis larvae can recognize and respond to the presence of progesterone through a molecule possibly able to bind it. Since we previously observed a similar response to prolactin, we suggest that both hormones could participate sequentially in the reactivation of T. canis larvae in pregnant bitches.


Subject(s)
Progesterone/pharmacology , Progestins/pharmacology , Receptors, Progesterone/drug effects , Toxocara canis/drug effects , Animals , Base Sequence , DNA, Helminth/chemistry , DNA, Helminth/isolation & purification , Dogs , Female , Flow Cytometry , Intestines/parasitology , Larva/drug effects , Larva/growth & development , Larva/physiology , Mice , Microscopy, Confocal , Movement/drug effects , Polymerase Chain Reaction , Receptors, Progesterone/analysis , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Toxocara canis/growth & development , Toxocara canis/physiology
17.
Infect Dis Poverty ; 7(1): 59, 2018 Jun 13.
Article in English | MEDLINE | ID: mdl-29895324

ABSTRACT

BACKGROUND: Toxocariasis is a neglected parasitic zoonosis that afflicts millions of the pediatric and adolescent populations worldwide, especially in impoverished communities. This disease is caused by infection with the larvae of Toxocara canis and T. cati, the most ubiquitous intestinal nematode parasite in dogs and cats, respectively. In this article, recent advances in the epidemiology, clinical presentation, diagnosis and pharmacotherapies that have been used in the treatment of toxocariasis are reviewed. MAIN TEXT: Over the past two decades, we have come far in our understanding of the biology and epidemiology of toxocariasis. However, lack of laboratory infrastructure in some countries, lack of uniform case definitions and limited surveillance infrastructure are some of the challenges that hindered the estimation of global disease burden. Toxocariasis encompasses four clinical forms: visceral, ocular, covert and neural. Incorrect or misdiagnosis of any of these disabling conditions can result in severe health consequences and considerable medical care spending. Fortunately, multiple diagnostic modalities are available, which if effectively used together with the administration of appropriate pharmacologic therapies, can minimize any unnecessary patient morbidity. CONCLUSIONS: Although progress has been made in the management of toxocariasis patients, there remains much work to be done. Implementation of new technologies and better understanding of the pathogenesis of toxocariasis can identify new diagnostic biomarkers, which may help in increasing diagnostic accuracy. Also, further clinical research breakthroughs are needed to develop better ways to effectively control and prevent this serious disease.


Subject(s)
Neglected Diseases , Public Health , Toxocara/physiology , Toxocariasis , Zoonoses , Animals , Cats , Dogs , Humans , Neglected Diseases/diagnosis , Neglected Diseases/drug therapy , Neglected Diseases/epidemiology , Neglected Diseases/parasitology , Toxocara canis/physiology , Toxocariasis/diagnosis , Toxocariasis/drug therapy , Toxocariasis/epidemiology , Toxocariasis/parasitology , Zoonoses/diagnosis , Zoonoses/drug therapy , Zoonoses/epidemiology , Zoonoses/parasitology
18.
Biosci Rep ; 38(4)2018 08 31.
Article in English | MEDLINE | ID: mdl-29921576

ABSTRACT

Toxocariasis is a zoonotic disease produced by ingestion of larval Toxocara spp. eggs. Prolactin (PRL) has been considered to have an important role in Toxocara canis infection. Recent evidence has found that PRL directly can increase parasite growth and differentiation of T. canis The present study, evaluated the effect of high PRL levels on the immune system's response and parasites clearance in chronic infection. Our results showed that hyperprolactinemia did not affect the number of larvae recovered from several tissues in rats. Parasite-specific antibody production, showed no difference between the groups. Lung tissue presented eosinophilic granulomas typical of a chronic infection in all the experimental groups. Flow cytometry analysis was made in order to determine changes in the percentage of innate and adaptive immune cell subpopulations in the spleen, peripheric (PLN) and mesenteric (MLN) lymphatic nodes. The results showed a differential effect of PRL and infection on different immune compartments in the percent of total T cells, T helper cells, T cytotoxic cells, B cells, NK cells, and Tγδ cells. To our knowledge, for the first time it is demonstrated that PRL can have an immunomodulatory role during T. canis chronic infection in the murine host.


Subject(s)
Prolactin/immunology , Toxocara canis/immunology , Toxocariasis/immunology , Adaptive Immunity , Animals , Host-Parasite Interactions , Immunity, Innate , Larva/immunology , Lung/immunology , Lung/parasitology , Lung/pathology , Male , Prolactin/analysis , Rats, Wistar , T-Lymphocytes/immunology , T-Lymphocytes/parasitology , T-Lymphocytes/pathology , Toxocara canis/physiology , Toxocariasis/blood , Toxocariasis/pathology , Zoonoses/blood , Zoonoses/immunology , Zoonoses/pathology
19.
Vet Parasitol ; 252: 173-179, 2018 Mar 15.
Article in English | MEDLINE | ID: mdl-29559144

ABSTRACT

Toxocara canis is the helminth causing Toxocariasis, a parasitic disease with medical and veterinary implications. Their final host are members of the family Canidae and as paratenic hosts, most of the mammals are sensitive (man, rat, mouse, among others). It has been reported that a pituitary hormone, prolactin, it is responsible for reactivation and migration of larvae to the uterus and mammary gland during the last third of gestation in bitches. In addition, this hormone has been shown to play an important role in the regulation of the immune response. Thus, the aim of this study, was to evaluate the effect of hypophysectomy in the rat model of Toxocariasis, on the immune response against this parasite during a chronic infection, for which parasite loads were analyzed in different organs (lung and brain). Furthermore, serum specific antibody titers, and percentages of different cells of the immune system were also determined. The results showed a decrease in the number of larvae recovered from lung and brain in the hypophysectomized animals. In this same group of animals, there was no production of specific antibodies against the parasite. As for the percentages of the cells of the immune system, there are differences in some subpopulations due to surgery and others due to infection. Our results demonstrated that the lack of pituitary hormones alters parasite loads and the immune response to the helminth parasite Toxocara canis.


Subject(s)
Chronic Disease , Pituitary Hormones/immunology , Toxocara canis/immunology , Toxocariasis/immunology , Toxocariasis/physiopathology , Animals , Antibodies, Helminth/blood , Brain/immunology , Brain/parasitology , Disease Models, Animal , Hypophysectomy , Larva/growth & development , Mice , Parasite Load , Pituitary Hormones/deficiency , Rats , Toxocara canis/physiology
20.
Parasitol Res ; 117(3): 775-782, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29423531

ABSTRACT

Toxocara canis is a zoonotic parasite with worldwide distribution. ATP-binding cassette (ABC) transporters are integral membrane proteins which involve in a range of biological processes in various organisms. In present study, the full-length coding sequence of abcg-5 gene of T. canis (Tc-abcg-5) was cloned and characterized. A 633 aa polypeptide containing two conserved Walker A and Walker B motifs was predicted from a continuous 1902 nt open reading frame. Quantitative real-time PCR was employed to determine the transcriptional levels of Tc-abcg-5 gene in adult male and female worms, which indicated high mRNA level of Tc-abcg-5 in the reproductive tract of adult female T. canis. Tc-abcg-5 was expressed to produce rabbit polyclonal antiserum against recombinant TcABCG5. Indirect-fluorescence immunohistochemical assays were carried out to detect the tissue distribution of TcABCG5, which showed predominant distribution of TcABCG5 in the uterus (especially in the germ cells) of adult female T. canis. Tissue transcription and expression pattern of Tc-abcg-5 indicated that Tc-abcg-5 might play essential roles in the reproduction of this parasitic nematode.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 5/biosynthesis , Toxocara canis/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics , Animals , Dog Diseases/parasitology , Dogs , Female , Male , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Reproduction , Tissue Distribution , Toxocara canis/isolation & purification , Toxocara canis/physiology , Toxocariasis/parasitology , Transcription, Genetic , Uterus/metabolism
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