Department of Pathology, Medical School, University of Texas-Houston Medical School, Houston, TX; Scholarly Concentration in Molecular and Translational Medicine, Houston, TX.
Department of Pathology, Medical School, University of Texas-Houston Medical School, Houston, TX.
Tuberculosis (Edinb). 2013 Dec;93 Suppl:S88-93. doi: 10.1016/S1472-9792(13)70017-9.
Presensitization with Mtb-derived trehalose 6,6'-dimycolate (TDM; cord factor) followed by challenge with the same glycolipid species resulted in elicitation of stronger inflammatory responses than when mice were similarly challenged with M. bovis-derived TDM. Mice presensitized to the homologous Mtb-derived TDM demonstrated cachexic over a 6 day period, whereas similarly presensitized mice challenged with the M. bovis-derived TDM, or with emulsion control, did not experience weight loss. Examination of inflammatory responses demonstrated increased lung histopathology in the Mtb-derived TDM challenged group, evidenced by severe tissue disruption, cellular influx, vascular occlusion and lymphocytic cuffing, and endothelial cell damage. Histological analysis demonstrated that lung pathology in the M. bovis challenged group was strikingly similar to that of the acute model challenge. Examination of proinflammatory mediators also showed findings consistent with histological manifestation, with significantly elevated TNF-α and IL-1β, as well as IFN-γ, in the homologous TDM challenged group relative to all other groups. Overall, these findings indicate a difference in hypersensitive immune responses to TDM derived from different mycobacterial strains. Development of specific adaptive immune responses to the Mtb-derived TDM were demonstrated that had limited cross-reactivity to that of M. bovis, thus strongly suggesting the presence of hypersensitive epitopes exclusive to Mtb TDM not present on M. bovis-derived TDM.
结核分枝杆菌海藻糖 6,6'-二分枝菌酸（TDM；索状因子）致敏后再用相同糖脂类物质进行攻毒，引发的炎症反应强于用牛分枝杆菌来源的 TDM 进行类似攻毒。用同源结核分枝杆菌来源的 TDM 致敏的小鼠在 6 天内出现恶病质，而用牛分枝杆菌来源的 TDM 或乳剂对照进行类似致敏的小鼠则没有体重减轻。炎症反应检查显示，用结核分枝杆菌来源的 TDM 攻毒的小鼠肺部组织病理学变化更为严重，表现为严重的组织破坏、细胞浸润、血管阻塞和淋巴细胞袖口形成以及内皮细胞损伤。组织学分析表明，牛分枝杆菌攻毒组的肺部病变与急性模型攻毒组的病变非常相似。促炎介质的检查也显示出与组织学表现一致的结果，与其他所有组相比，同源 TDM 攻毒组的 TNF-α和 IL-1β以及 IFN-γ显著升高。总之，这些发现表明对来自不同分枝杆菌菌株的 TDM 的超敏免疫反应存在差异。对来自结核分枝杆菌的 TDM 产生的特定适应性免疫反应的发展表明，对牛分枝杆菌来源的 TDM 的交叉反应有限，这强烈表明存在结核分枝杆菌 TDM 特有的、牛分枝杆菌来源的 TDM 中不存在的超敏表位。
