Dong Haodi, Lv Yue, Sreevatsan Srinand, Zhao Deming, Zhou Xiangmei
State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and College of Veterinary Medicine, China Agricultural University, Beijing, China.
Veterinary Population Medicine Department, College of Veterinary Medicine, University of Minnesota, St Paul, MN, United States of America.
PLoS One. 2017 Aug 24;12(8):e0183666. doi: 10.1371/journal.pone.0183666. eCollection 2017.
Animal mycobacterioses are among the most important zoonoses worldwide. These are generally caused by either Mycobacterium tuberculosis (MTB), M. bovis (MBO) or M. avium (MAV). To test the hypothesis that different species of pathogenic mycobacteria isolated from varied anatomic locations or animal species differ in virulence and pathogenicity, we performed experiments with three mycobacteria strains (NTSE-3(MTB), NTSE-4(MBO) and NTSE-5 (MAV)) obtained from animal species. Spoligotyping analysis was used to confirm both MTB and MBO strains while the MAV strain was confirmed by 16s rDNA sequencing. BALB/c mice were intranasally infected with the three strains at low and high CFU doses to evaluate variations in pathogenicity. Clinical and pathological parameters were assessed. Infected mice were euthanized at 80 days post-inoculation (dpi). Measures of lung and body weights indicated that the MBO infected group had higher mortality, more weight loss, higher bacterial burden and more severe lesions in lungs than the other two groups. Cytokine profiles showed higher levels of TNF-α for MBO versus MTB, while MAV had the highest amounts of IFN-β in vitro and in vivo. In vitro levels of other cytokines such as IL-1β, IL-10, IL-12, IL-17, and IFN-β showed that Th1 cells had the strongest response in MBO infected mice and that Th2 cells were inhibited. We found that the level of virulence among the three isolates decreased in the following order MBO>MTB>MAV.
动物分枝杆菌病是全球最重要的人畜共患病之一。这些疾病通常由结核分枝杆菌(MTB)、牛分枝杆菌(MBO)或鸟分枝杆菌(MAV)引起。为了验证从不同解剖部位或动物物种分离出的不同致病性分枝杆菌在毒力和致病性方面存在差异这一假设,我们用从动物物种获得的三种分枝杆菌菌株(NTSE - 3(MTB)、NTSE - 4(MBO)和NTSE - 5(MAV))进行了实验。 spoligotyping分析用于确认MTB和MBO菌株,而MAV菌株通过16s rDNA测序进行确认。将BALB/c小鼠经鼻内以低和高CFU剂量感染这三种菌株,以评估致病性的差异。评估临床和病理参数。在接种后80天(dpi)对感染小鼠实施安乐死。肺和体重测量表明,与其他两组相比,MBO感染组的死亡率更高、体重减轻更多、细菌载量更高且肺部病变更严重。细胞因子谱显示,MBO组的TNF-α水平高于MTB组,而MAV在体外和体内的IFN-β含量最高。其他细胞因子如IL - 1β、IL - 10、IL - 12、IL - 17和IFN-β的体外水平表明,Th1细胞在MBO感染小鼠中的反应最强,而Th2细胞受到抑制。我们发现,三种分离株的毒力水平按以下顺序降低:MBO>MTB>MAV。