Bovine tuberculosis (bTB) caused by Mycobacterium bovis has a significant economic impact worldwide each year. Control of bTB is based on skin testing and removal of reactors. However, additional strategies are required to control this disorder. Natural disease resistance has been defined as the inherent capacity of an individual to resist disease when exposed to pathogens without previous exposure or immunization. However, little is known about natural disease resistance against Mycobacterium bovis in cattle. In this study, we aimed to identify candidate biomarkers to detect host resistance to M. bovis. We used a microbicidal assay to identify the resistance phenotype. A genomic microarray analysis was carried out on RNA from 2 resistant (R) and 2 susceptible (S) cows. Our results evidenced 69 differentially expressed genes. A subset of six genes that showed differential up (IL1RN), and down-regulation (VNN, GATM, ARHGEF11, NAAA and HSPA2) were selected for further analysis. To further validate the candidate biomarkers, we identified the R phenotype in 31 cattle (9 R and 22 S). Macrophage mRNA was isolated from this group of cattle. Expression of candidate biomarkers was evaluated by qPCR 2-ΔCt and ROC curves to determine their diagnostic potential. Candidates IL1RN and ARHGEF11 discriminates between R and S cattle. Furthermore, combination of candidates ARHGEF11: VNN: HSPA2 discriminate between R from S with AUC 0.7993 and agreement index of 0.853 (p ≤ 0.01). Our data suggest that candidate biomarkers may support the preliminary screening to identify natural resistance in herds against Mycobacterium bovis in Holstein-Friesian cattle.
Keywords: Biomarkers; Bovine tuberculosis; Microbicidal assay; Resistance; Susceptibility.
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.