Unraveling coagulopathies in Angiostrongylus vasorum-infected dogs using a transcriptomic approach
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ABSTRACT:
PROVIDER: PRJEB53546 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR9849220.fastq.gz | Fastqsanger.gz | |||
| ERR9849230.fastq.gz | Fastqsanger.gz | |||
| ERR9849221.fastq.gz | Fastqsanger.gz | |||
| ERR9849231.fastq.gz | Fastqsanger.gz | |||
| ERR9849222.fastq.gz | Fastqsanger.gz |
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Project description:Molecular characterisation of Angiostrongylus vasorum from UK foxes
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Project description:Angiostrongylus vasorum strain:ZH-2019-22 Genome sequencing and assembly
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Project description:Dogs infected with the cardiopulmonary nematode Angiostrongylus vasorum may suffer respiratory distress and/or bleeding disorders. Descriptions of clinical signs in foxes are rare, despite high prevalence. To evaluate the impact of infection on coagulation and immune response, serum proteins from eight experimentally infected foxes before and after inoculation (day 0, 35, 84, 154) were subjected to quantitative proteomic analysis and compared to available data from dogs. The number of differentially expressed proteins compared to uninfected baseline increased with chronicity of the infection. Bone marrow proteoglycan, chitinase 3-like protein 1 and pulmonary surfactant-associated protein B were among strongly upregulated proteins. Several proteins involved in coagulation were downregulated. Enriched pathways obtained from both up- and downregulated proteins included among others ‘platelet degranulation‘ and ‘haemostasis’, and indicated both activation and suppression of coagulation. Qualitative comparison to dog data suggests some parallel serum proteomic alterations. The comparison, however, highlights that foxes have a more balanced immunopathological response to A. vasorum infection compared to dogs, facilitating parasite survival in foxes. Our findings imply that foxes may cope better with an A. vasorum infection and that A. vasorum is likely more adapted to foxes as compared to dogs, explaining the relevant role of foxes as wildlife reservoir.
2021-11-25 | PXD028312 | Pride
Project description:Systemic infection by Angiostrongylus vasorum in a fennec (Vulpes zerda) in an Italian zoological garden
| PRJEB55043 | ENA
Project description:Angiostrongylus vasorum is a cardiopulmonary nematode of canids and is, among others associated with bleeding disorders in dogs. The pathogenesis of coagulopathies remains unclear. We performed a deep proteomic characterization of sex specific A. vasorum excretory/secretory proteins (ESP) and of cuticular surface proteins, and evaluated the effect of ESP on host coagulation and fibrinolysis in vitro. Proteins were quantified by liquid chromatography coupled to mass spectrometry and functionally characterized through gene ontology and pathway enrichment analysis. In total, we identified 1069 ESP (944 from female and 959 from male specimens) and 1195 surface proteins (705 and 1135, respectively). Among these, we identified putative modulators of host coagulation, e.g., von Willebrand factor type D domain protein orthologues as well as several proteases, including serine type proteases, protease inhibitors and proteasome subunits. The effect of ESP on dog coagulation and fibrinolysis was evaluated on canine endothelial cells and by rotational thromboelastometry (ROTEM). After stimulation with ESP, tissue factor and serpin E1 transcript expression increased. ROTEM revealed minimal interaction of ESP with dog blood and did not influence the onset of fibrinolysis. We thus conclude that Angiostrongylus vasorum ESP and surface proteins do not act alone in the induction of bleeding in dogs. The interaction with the host’s vascular haemostasis is limited. It is likely that coagulopathies in A. vasorum infected dogs are the result of a multifactorial response of the host to this parasitic infection.
2021-11-03 | PXD027520 | Pride
Project description:Infection by Angiostrongylus cantonensis accounted for the meningitis characterized by accumulation of eosinophils in non-permissive host like mouse and human. However, the underlying molecular basis is still obscure. To uncover the specific molecular mechanism responsible for the meningitis caused by Angiostrongylus cantonensis, we carried out gene expression array for mouse brain with infection by Angiostrongylus cantonensis.
2020-10-14 | GSE159486 | GEO
Project description:Blood contains hundreds of proteins, reflecting ongoing cellular processes and immune reactions. Angiostrongylus vasorum infection is associated with a perturbed blood protein profile in dogs. However, the literature currently available lacks the necessary depth of analysis in order to resolve the observed pathologies in A. vasorum infections, including bleeding disorders. Using sera from 8 experimentally-infected dogs (i) before infection with A. vasorum, (ii) 34 days post-infection (p.i.; immature infection), and (iii) 75 days p.i. (mature patent infection), serum proteins were measured using liquid chromatography, tandem mass spectrometry (LC-MS/MS). For 2 dogs, serum was analyzed at days 104 and 230 p.i. additionally. A data-independent acquisition workflow was employed in order to generate quantitative data. Following computational analysis, we identified 139 up- and down-regulated proteins following infection (log2 ratio cutoff ≥ 1.0; q-value ≤ 0.05). Differences in serum profiles were most pronounced at day 75 p.i. compared to before infection. Among up-regulated proteins, chitinase 3, several saposin-like proteins, and heat shock proteins were found greatly increased (log2 fold-changes ≥ 5). Levels of pulmonary surfactant protein B were elevated on day 34 p.i. already, in the prepatent phase. Pathway enrichment revealed that complement (especially the lectin pathway) and coagulation cascades as significantly affected upon analysis of down-regulated proteins. Among them were mannan-binding lectin serine peptidases, ficolin, and coagulation factors. These results reflect the ongoing immune response and stress imposed to the lungs by the parasite. In addition, they bring new elements towards understanding the coagulopathies observed in some A. vasorum-infected dogs.
2021-01-12 | PXD016881 | Pride
Project description:BackgroundThe pathomechanism of Angiostrongylus vasorum infection-associated bleeding diathesis in dogs is not fully understood.ObjectiveTo describe rotational thromboelastometry (ROTEM) parameters in dogs naturally infected with A. vasorum and to compare ROTEM parameters between infected dogs with and without clinical signs of bleeding.AnimalsA total of 21 dogs presented between 2013 and 2016.MethodsDogs with A. vasorum infection and ROTEM evaluation were retrospectively identified. Thrombocyte counts, ROTEM parameters, clinical signs of bleeding, therapy, and survival to discharge were retrospectively retrieved from patient records and compared between dogs with and without clinical signs of bleeding.ResultsEvaluation by ROTEM showed hyperfibrinolysis in 8 of 12 (67%; 95% CI, 40-86%) dogs with and 1 of 9 (11%; 95% CI, 2-44%) dogs without clinical signs of bleeding (P = .016). Hyperfibrinolysis was associated with severe hypofibrinogenemia in 6 of 10 (60%; 95% CI, 31-83%) of the cases. Hyperfibrinolysis decreased or resolved after treatment with 10-80 mg/kg tranexamic acid. Fresh frozen plasma (range, 14-60 mL/kg) normalized follow-up fibrinogen function ROTEM (FIBTEM) maximal clot firmness in 6 of 8 dogs (75%; 95% CI, 41-93%). Survival to discharge was 67% (14/21 dogs; 95% CI, 46-83%) and was not different between dogs with and without clinical signs of bleeding (P = .379).Conclusion and clinical importanceHyperfibrinolysis and hypofibrinogenemia were identified as an important pathomechanism in angiostrongylosis-associated bleeding in dogs. Hyperfibrinolysis and hypofibrinogenemia were normalized by treatment with tranexamic acid and plasma transfusions, respectively.
| S-EPMC5508311 | biostudies-literature
Project description:BackgroundAngiostrongylus vasorum is a nematode living in the pulmonary arteries of canids. Infected dogs develop severe pulmonary lesions which can potentially lead to pulmonary hypertension (PH). However, reports of PH in natural infected dogs are scant. One of the possible causes of the low prevalence of PH in A. vasorum-infected dogs could be the establishment of large diameter intrapulmonary arteriovenous anastomoses (IPAVAs), which attenuate pulmonary vascular resistance, thus reducing the pulmonary arterial pressure. The present report describes the pulmonary arterial pressure (PAP) response to A. vasorum natural infection in two dogs, assessed by echocardiography and by the saline contrast echocardiographic test (SCE).ResultsBoth dogs showed clinical signs of respiratory disease. At presentation, case 1 did not show echocardiographic signs of PH and the SCE test was positive proving the presence of IPAVAs. However, at the follow-up visit, despite A. vasorum infection resolution, the same dog showed PH and the SCE test resulted negative, which ruled out the presence of IPAVAs. Case 2 suffered from severe pulmonary arterial hypertension and right-side congestive heart failure since the day of presentation. Saline contrast echocardiography was negative both at the time of presentation and at the follow-up visit.ConclusionsIn the two cases described above, the PH was not associated with IPAVAs. During A. vasorum infection, IPAVAs recruitment mechanism is able to contrast the rise of PAP until a certain level. It probably represents an initial escape mechanism of PH that, over time, exhausts its compensatory capacities allowing PAP to rise and to be detectable on echocardiography.
| S-EPMC6549332 | biostudies-literature