Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Nat Commun. 2023 Sep 20;14(1):5840. doi: 10.1038/s41467-023-41519-9.
Diabetes mellitus increases risk for tuberculosis disease and adverse outcomes. Most people with both conditions have type 2 diabetes, but it is unknown if type 1 and type 2 diabetes have identical effects on tuberculosis susceptibility. Here we show that male mice receiving a high-fat diet and streptozotocin to model type 2 diabetes, have higher mortality, more lung pathology, and higher bacterial burden following Mycobacterium tuberculosis infection compared to mice treated with streptozotocin or high-fat diet alone. Type 2 diabetes model mice have elevated plasma glycerol, which is a preferred carbon source for M. tuberculosis. Infection studies with glycerol kinase mutant M. tuberculosis reveal that glycerol utilization contributes to the susceptibility of the type 2 diabetes mice. Hyperglycemia impairs protective immunity against M. tuberculosis in both forms of diabetes, but our data show that elevated glycerol contributes to an additional adverse effect uniquely relevant to type 2 diabetes.
糖尿病会增加结核病发病风险和不良预后。大多数合并这两种疾病的患者都患有 2 型糖尿病，但目前尚不清楚 1 型和 2 型糖尿病是否对结核病易感性有相同的影响。在这里，我们发现接受高脂肪饮食和链脲佐菌素治疗以模拟 2 型糖尿病的雄性小鼠，与单独接受链脲佐菌素或高脂肪饮食治疗的小鼠相比，在感染结核分枝杆菌后死亡率更高、肺部病变更多且细菌负荷更高。2 型糖尿病模型小鼠的血浆甘油水平升高，甘油是结核分枝杆菌的首选碳源。用甘油激酶突变的结核分枝杆菌进行的感染研究表明，甘油利用有助于 2 型糖尿病小鼠的易感性。高血糖会损害两种类型糖尿病患者对结核分枝杆菌的保护性免疫，但我们的数据表明，甘油水平升高会导致一种独特的、与 2 型糖尿病相关的额外不良影响。
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