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.

牛分枝杆菌引起的牛结核病（bTB）每年在全球范围内都具有重大的经济影响。bTB的控制基于皮肤测试和移除反应堆。但是，需要其他策略来控制这种疾病。天然疾病抗性已被定义为个体暴露于病原体而没有事先暴露或免疫的情况下抵抗疾病的固有能力。然而，关于牛的牛分枝杆菌的天然抗病性知之甚少。在这项研究中，我们旨在鉴定候选生物标志物以检测宿主对牛分枝杆菌的抗性。我们使用了杀微生物试验来鉴定抗性表型。对来自2头抗性（R）和2例易感（S）母牛的RNA进行了基因组微阵列分析。我们的结果证明了69个差异表达的基因。选择了六个基因的子集，这些基因表现出差异上调（IL1RN）和下调（VNN，GATM，ARHGEF11，NAAA和HSPA2）进行进一步分析。为了进一步验证候选生物标记，我们在31头牛（9 R和22 S）中鉴定了R表型。从这组牛中分离出巨噬细胞mRNA。通过qPCR 2- ^ΔCt评估候选生物标志物的表达和ROC曲线确定其诊断潜力。候选IL1RN和ARHGEF11区分R和S牛。此外，候选的组合ARHGEF11：VNN：从S R与AUC 0.7993和0.853（协议索引之间HSPA2判别p  ≤0.01）。我们的数据表明，候选生物标志物可能支持初步筛选，以鉴定牛群中对荷斯坦-弗里斯牛的牛分枝杆菌的自然抗性。