Tuberculosis (TB)-type 2 diabetes mellitus (T2D) comorbidity is re-emerging as a global public health problem. T2D is a major risk factor for increased susceptibility to TB infection and reactivation leading to higher morbidity and mortality. The pathophysiological mechanisms of T2D contributing to TB susceptibility are not fully understood, but likely involve dysregulated immune responses. In this study, a diet-induced murine model that reflects the cardinal features of human T2D was used to assess the immune responses following an intravenous Mycobacterium tuberculosis (Mtb) infection. In this study, T2D significantly increased mortality, organ bacillary burden and inflammatory lesions compared to non-diabetic controls. Organ-specific pro-inflammatory cytokine responses were dysregulated as early as one day post-infection in T2D mice. Macrophages derived from T2D mice showed reduced bacterial internalization and killing capacity. An early impairment of antimycobacterial functions of macrophages in diabetes is a key mechanism that leads to increased susceptibility of T2D.

结核（TB）2型糖尿病（T2D）合并症正在作为全球公共卫生问题重新出现。T2D是增加对结核病感染和再激活的敏感性的主要危险因素，导致更高的发病率和死亡率。T2D导致结核病易感性的病理生理机制尚不完全清楚，但可能涉及免疫反应失调。在这项研究中，饮食诱导的鼠模型反映了人类T2D的主要特征，用于评估静脉分枝杆菌（Mtb）后的免疫反应。） 感染。在这项研究中，与非糖尿病对照组相比，T2D显着增加了死亡率，器官细菌负担和炎性病变。最早在T2D小鼠感染后一天，器官特异性促炎细胞因子反应就失调了。源自T2D小鼠的巨噬细胞显示细菌内在化和杀伤能力降低。糖尿病中巨噬细胞抗分枝杆菌功能的早期损害是导致T2D易感性增加的关键机制。