Instituto de Investigación en Recursos Cinegéticos IREC (CSIC-UCLM-JCCM), Ronda de Toledo s/n, 13005 Ciudad Real, Spain.
Med Hypotheses. 2011 Mar;76(3):361-4. doi: 10.1016/j.mehy.2010.10.040. Epub 2010 Nov 16.
Bovine tuberculosis (bTB) is a disease caused by Mycobacterium bovis and closely related species of the Mycobacterium tuberculosis complex. bTB is an important health problem affecting livestock, wild animals and accounting for up to 10% of human TB cases worldwide. Several hypotheses have been considered to explain the low incidence of active TB despite high infection rates and the variable response to BCG vaccination. These hypotheses have considered genetic factors of immunized individuals and BCG strains, sensitization to environmental mycobacteria and metabolic processes. However, a link has not been established between genetic factors and metabolic processes that may affect the outcome of M. bovis infection and response to BCG vaccination. Herein we used published data linking host cholesterol metabolism with mycobacterial infection, persistence and disease outcome, and results obtained from studies of M. bovis infection and BCG vaccination in the wild boar bTB model to propose a hypothesis: host genetically-defined higher host methylmalonyl-CoA mutase (MUT) expression levels result in lower serum cholesterol concentration and tissue deposits that increase the protective immune response to M. bovis, thus resulting in resistance to bTB and better response to BCG vaccination. If the hypothesis is proven true, these results have important implications for the prevention and treatment of bTB in humans and for the eradication of bTB in wildlife reservoir hosts.
牛结核病（bTB）是由牛分枝杆菌和与其密切相关的结核分枝杆菌复合群引起的疾病。bTB 是影响牲畜、野生动物的一个重要健康问题，占全球人类结核病病例的 10%。尽管感染率高，卡介苗接种的反应各不相同，但有几个假说被认为可以解释结核病的低发病率。这些假说考虑了免疫个体和卡介苗菌株的遗传因素、对环境分枝杆菌的致敏和代谢过程。然而，尚未确定遗传因素和代谢过程之间的联系，这些因素可能影响牛分枝杆菌感染的结果和卡介苗接种的反应。在此，我们使用了已发表的数据，将宿主胆固醇代谢与分枝杆菌感染、持续存在和疾病结果联系起来，并从野猪 bTB 模型中的牛分枝杆菌感染和卡介苗接种研究中获得的结果，提出了一个假说：宿主遗传定义的较高的甲基丙二酰辅酶 A 变位酶（MUT）表达水平导致血清胆固醇浓度降低和组织沉积增加，从而增强对牛分枝杆菌的保护性免疫反应，进而导致对 bTB 的抵抗力增强和对卡介苗接种的反应更好。如果这一假说被证明是正确的，这些结果对于预防和治疗人类 bTB 以及消除野生动物宿主中的 bTB 具有重要意义。
