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Fox serum proteomics analysis suggests host-specific responses to Angiostrongylus vasorum infection

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Vulpes Vulpes (red Fox)

TISSUE(S): Blood Serum

SUBMITTER: Nina Gillis

LAB HEAD: Manuela Schnyder

PROVIDER: PXD028312 | Pride | 2021-11-25

REPOSITORIES: Pride

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			Action	DRS
	20200616_002_S218519_22_2_d0_Group_1.raw	Raw
	20200616_003_S218524_27_44_d84_Group_3.raw	Raw
	20200616_004_S218511_14_40_d35_Group_2.raw	Raw
	20200616_005_S218521_24_7_d84_Group_3.raw	Raw
	20200616_006_S218499_2_40_d0_Group_1.raw	Raw

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Project description:Introduction: The relationship between epilepsy and cognitive dysfunction has been investigated in canines, and memory impairment was prevalent in dogs with epilepsy. There is some evidence that canines with epilepsy have greater amyloid-β (Aβ) accumulation and neuronal degeneration than healthy controls. The present study investigated plasma Aβ42 levels and performed proteomic profiling in dogs with refractory epilepsy and healthy dogs. Methods: In total, eight dogs, including four healthy dogs and four dogs with epilepsy, were included in the study. Blood samples were collected to analyze Aβ42 levels and perform proteomic profiling. Changes in the plasma proteomic profiles of dogs were determined by nano LC-MS/MS. Results and discussion: The plasma Aβ42 level was significantly higher in dogs with epilepsy (99 pg/mL) than in healthy dogs (5.9 pg/mL). In total, 155 proteins were identified, and of these, the expression of 40 proteins was altered in epilepsy. Among these proteins, which are linked to neurodegenerative diseases, 10 (25%) were downregulated in dogs with epilepsy, whereas 12 (30%) were upregulated. The expression of the acute phase proteins haptoglobin and α2-macroglobulin significantly differed between the groups. Complement factor H and ceruloplasmin were only detected in epilepsy dogs, suggesting that neuroinflammation plays a role in epileptic seizures. Gelsolin, which is involved in cellular processes and cytoskeletal organization, was only detected in healthy dogs. Gene Ontology annotation revealed that epilepsy can potentially interfere with biological processes, including cellular processes, localization, and responses to stimuli. Seizures compromised key molecular functions, including catalytic activity, molecular function regulation, and binding. Defense/immunity proteins were most significantly modified during the development of epilepsy. In Kyoto Encyclopedia of Genes and Genomes pathway analysis, complement and coagulation cascades were the most relevant signaling pathways affected by seizures. The findings suggested that haptoglobin, ceruloplasmin, α2-macroglobulin, complement factor H, and gelsolin play roles in canine epilepsy and Aβ levels based on proteomic profiling. These proteins could represent diagnostic biomarkers that, after clinical validation, could be used in veterinary practice as well as proteins relevant to disease response pathways. To determine the precise mechanisms underlying these relationships and their implications in canine epilepsy, additional research is required.

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Fox serum proteomics analysis suggests host-specific responses to Angiostrongylus vasorum infection

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