BCG vaccination reduces the mortality of Mycobacterium tuberculosis-infected type 2 diabetes mellitus mice.
BCG vaccination reduces the mortality of Mycobacterium tuberculosis-infected type 2 diabetes mellitus mice.
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BCG 疫苗接种可降低结核分枝杆菌感染的 2 型糖尿病小鼠的死亡率。
DOI：
10.1172/jci.insight.133788
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发表时间：
2020
期刊：
影响因子：
8
通讯作者：
Vankayalapati,Ramakrishna
中科院分区：
文献类型：
--
作者：
Radhakrishnan,RajeshKumar;Thandi,RamyaSivangala;Tripathi,Deepak;Paidipally,Padmaja;McAllister,MadelineKay;Mulik,Sachin;Samten,Buka;Vankayalapati,Ramakrishna
糖尿病是活动性肺结核发病的重要危险因素。在这项研究中，我们使用2型糖尿病（T2DM）小鼠模型来确定事先接种卡介苗（BCG）对结核分枝杆菌（Mtb）感染免疫应答的影响。我们发现，在结核分枝杆菌感染6-7个月后，90%感染结核分枝杆菌的T2DM小鼠死亡，而接种bcg的T2DM-结核分枝杆菌感染小鼠只有50%死亡。此外，接受pbs治疗的未感染T2DM小鼠中有40%死亡，接种bcg的未感染T2DM小鼠中有30%死亡，而未感染和感染的非糖尿病小鼠全部存活。与mtb感染的非糖尿病小鼠相比，卡介苗接种在减少mtb感染的T2DM小鼠肺部细菌负担方面效果较差。与未接种结核分枝杆菌的T2DM小鼠相比，接种卡介苗可显著降低结核分枝杆菌感染T2DM小鼠的肺部炎症。此外，接种bcg的mtb感染T2DM小鼠的死亡率降低与mtb感染T2DM小鼠肺中产生il -13的CXCR3+ Tregs扩增有关。重组IL-13和Tregs可将促炎M1巨噬细胞转化为抗炎M2巨噬细胞。我们的研究结果提示卡介苗在预防结核分枝杆菌感染T2DM小鼠的过度炎症和死亡率方面具有潜在的新作用。
Diabetes is a significant risk factor for the development of active tuberculosis. In this study, we used a mouse model of type 2 diabetes mellitus (T2DM) to determine the effect of prior Bacillus Calmette-Guérin (BCG) vaccination on immune responses to Mycobacterium tuberculosis (Mtb) infection. We found that, at 6–7 months after Mtb infection, 90% of the Mtb-infected T2DM mice died, whereas only 50% of BCG-vaccinated T2DM-Mtb–infected mice died. Moreover, 40% of the PBS-treated uninfected T2DM mice and 30% of the uninfected BCG-vaccinated T2DM mice died, whereas all uninfected and infected nondiabetic mice survived. BCG vaccination was less effective in reducing the lung bacterial burden of Mtb-infected T2DM mice compared with Mtb-infected nondiabetic mice. BCG vaccination significantly reduced lung inflammation in Mtb-infected T2DM mice compared with that of unvaccinated T2DM mice infected with Mtb. Furthermore, reduced mortality of BCG-vaccinated Mtb-infected T2DM mice is associated with expansion of IL-13–producing CXCR3+ Tregs in the lungs of Mtb-infected T2DM mice. Recombinant IL-13 and Tregs from BCG-vaccinated Mtb-infected T2DM mice converted proinflammatory M1 macrophages to antiinflammatory M2 macrophages. Our findings suggest a potentially novel role for BCG in preventing excess inflammation and mortality in T2DM mice infected with Mtb.
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