Association between High Interferon-Gamma Production in Avian Tuberculin-Stimulated Blood from Mycobacterium avium subsp. paratuberculosis-Infected Cattle and Candidate Genes Implicated in Necroptosis
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Published:2023-07-15
Issue:7
Volume:11
Page:1817
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ISSN:2076-2607
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Container-title:Microorganisms
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language:en
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Short-container-title:Microorganisms
Author:
Badia-Bringué Gerard12ORCID, Canive María1, Vázquez Patricia1, Garrido Joseba M.1, Fernández Almudena3, Juste Ramón A.1ORCID, Jiménez José Antonio4ORCID, González-Recio Oscar3ORCID, Alonso-Hearn Marta1
Affiliation:
1. Department of Animal Health, NEIKER-Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160 Derio, Spain 2. Doctoral Program in Molecular Biology and Biomedicine, Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU), 48940 Leioa, Spain 3. Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Científicas, 28040 Madrid, Spain 4. CONAFE—Spanish Confederation of Holstein Cattle, 28009 Madrid, Spain
Abstract
The mechanisms underlying host resistance to Mycobacterium avium subsp. paratuberculosis (MAP) infection are largely unknown. In the current study, we hypothesize that cows with an ability to produce higher levels of interferon-gamma (IFNɣ) might control MAP infection more successfully. To test this hypothesis, IFNɣ production was measured using a specific IFNɣ ELISA kit in avian purified protein derivative (aPPD)-stimulated blood samples collected from 152 Holstein cattle. DNA isolated from peripheral blood samples of the animals included in the study was genotyped with the EuroG Medium-Density Bead Chip, and the genotypes were imputed to whole-genome sequencing. A genome-wide association analysis (GWAS) revealed that high levels of IFNɣ in response to the aPPD were associated with a specific genetic profile (heritability = 0.64) and allowed the identification of 71 SNPs, 40 quantitative trait loci (QTL), and 104 candidate genes. A functional analysis using the 104 candidate genes revealed a significant enrichment of genes involved in the innate immune response and, more specifically, in necroptosis. Taken together, our results define a heritable and distinct immunogenetic profile associated with the production of high IFNɣ levels and with the capacity of the host to lyse MAP-infected macrophages by necroptosis.
Subject
Virology,Microbiology (medical),Microbiology
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