Dataset Information

Quantitative proteomics analysis of Angiostrongylus vasorum-induced alterations in dog serum

ABSTRACT: 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.

ORGANISM(S): Canis Lupus Familiaris

SUBMITTER: Tobias Kockmann

PROVIDER: PXD016887 | panorama | Sun Jan 24 00:00:00 GMT 2021

REPOSITORIES: PanoramaPublic

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Publications

Quantitative proteomics analysis of Angiostrongylus vasorum-induced alterations in dog serum sheds light on the pathogenesis of canine angiostrongylosis.

Tritten Lucienne L Gillis-Germitsch Nina N Kockmann Tobias T Schnyder Manuela M

Scientific reports 20210111 1

Blood contains hundreds of proteins, reflecting ongoing cellular processes and immune reactions. Infections with the blood-dwelling cardiopulmonary nematode Angiostrongylus vasorum in dogs manifest with a broad spectrum of clinical signs including respiratory distress, bleeding diathesis and neurological signs, and are associated with a perturbed blood protein profile in dogs. However, current knowledge does not completely explain the observed pathologies induced by A. vasorum infections, includ ...[more]

PMID: 33431914

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Project description:Mycobacterium avium subspecies paratuberculosis (MAP) infection is established following the ingestion of bacteria, their penetration of the intestinal mucosa and subsequent events of the host-parasite interaction. These bacteria invade M cells, macrophages and are capable of resisting host defenses and multiply to reach very high numbers intracellular. Mycobactrium avium subsp. avium (MAA) is an antigenically and genetically similar organisms but is relatively nonpathogenic for cattle. MAA organisms appear to infect cattle, but unlike cattle infected with MAP, cattle infected with MAA typically mount an effective systemic immune response, form caseous granuloma, and eliminate the infection. This study was designed to understand the similarities and differences in the host responses during MAP and MAA infection. Neonatal calves were infected (ligated ileal loops) with PBS, MAP, or avirulent MAA following which samples were collected at 30 min, 1h, 2h, 4h, 8h, or 12h. Post-infection, RNA was collected, processed, and then hybridized to custom bovine gene expression arrays, each of which represented 13,258 transcripts spotted in duplicate. Arrays were normalized by scaling against the average reference intensity value (i.e., average across all arrays), normalized by global mean, and then log transformed before statistical analyses were performed. Pairwise comparisons of averaged signal values and Student’s t test were performed using GeneSifter software (VizX Labs, Seattle, WA). A fold-change of at least 1.5-fold and a p value of 0.05 or less was required for a difference in signal to be considered statistically significant. When comparing the transcriptional responses of calves infected with the MAA versus MAP, unique patterns of expression were clearly visible. In general, numbers of transcripts altered in response to infection were much greater for MAA-infected animals than for those infected with the MAP. No genes were significantly up-regulated in MAP-infected animals at the earliest time point tested (30 min), and only modest numbers of genes were increased in expression over the experimental time course. On the other hand, up-regulated transcripts were detected by 30 min in MAA-infected animals and peaked by 2 hr. Differences in the numbers of down-regulated genes between MAP-infected and MAA-infected animals (compared to PBS-infected controls) were less pronounced. At the earliest time points, MAP-infected calves had a greater number of down-regulated genes than did animals infected with MAA. This trend was reversed at 8 and 12 hr post-infection. Keywords: Gene expression profiling by microarray

Dataset Information

Quantitative proteomics analysis of Angiostrongylus vasorum-induced alterations in dog serum

Publications

Quantitative proteomics analysis of Angiostrongylus vasorum-induced alterations in dog serum sheds light on the pathogenesis of canine angiostrongylosis.

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