Faisal Shah, Vats Deepak, Panda Sudhasini, Sharma Vidushi, Luthra Kalpana, Mohan Anant, Kulkarni Savita, Gupta Pramod Kumar, Singh Archana
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India.
Department of Pulmonary Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India.
Tuberculosis (Edinb). 2024 Dec;149:102571. doi: 10.1016/j.tube.2024.102571. Epub 2024 Oct 15.
Host-directed therapies (HDT) via modulation of specific host responses like inflammation can limit mycobacterial infection. HDTs could be included in current TB therapy as an adjunct to increase bacterial clearance and limit tissue damage to control spread. Individually, Mycobacterium indicus pranii (MIP) and human beta defensin-2 (hBD-2) are promising therapies for tuberculosis (TB). They can directly target the TB bacilli and enhance cell-mediated immune responses, which is limiting with conventional drugs. Therefore, our study investigated the combined application of MIP and hBD-2 to evaluate their efficacy in clearing infections caused by Mycobacterium smegmatis (M.smeg) and Mycobacterium tuberculosis (M.tb) (both avirulent; H37Ra and virulent strain; H37Rv) in THP-1 cells and human monocyte-derived macrophages (MDMs). A strong pro-inflammatory response was observed against the combination of MIP and hBD-2 which also correlated with a significant reduction in the bacterial load. This combination further showed protection against M.tb by enhancing pyroptosis in the infected cells. The study suggests the combined use of these potent immunomodulators, which could be employed as an effective mode of therapy as adjuvants against mycobacterial infections after validation in a suitable animal model.
通过调节炎症等特定宿主反应的宿主导向疗法（HDT）可以限制分枝杆菌感染。HDT可作为辅助手段纳入当前的结核病治疗中，以增加细菌清除率并限制组织损伤，从而控制传播。单独来看，耻垢分枝杆菌（MIP）和人β-防御素2（hBD-2）都是有前景的结核病治疗方法。它们可以直接靶向结核杆菌并增强细胞介导的免疫反应，而这是传统药物所缺乏的。因此，我们的研究调查了MIP和hBD-2的联合应用，以评估它们在清除耻垢分枝杆菌（M.smeg）和结核分枝杆菌（M.tb）（无毒株；H37Ra和有毒株；H37Rv）在THP-1细胞和人单核细胞衍生巨噬细胞（MDM）中引起的感染方面的疗效。观察到针对MIP和hBD-2组合的强烈促炎反应，这也与细菌载量的显著降低相关。这种组合通过增强感染细胞中的细胞焦亡进一步显示出对M.tb的保护作用。该研究表明联合使用这些有效的免疫调节剂，在合适的动物模型中验证后，可作为抗分枝杆菌感染的有效治疗辅助手段。
