Mekong Health Science Research Institute, Khon Kaen, Thailand.
Faculty of Associated Medical Sciences, The Centre for Research and Development of Medical Diagnostic Laboratories, Khon Kaen University, Khon Kaen, Thailand.
Front Immunol. 2018 Sep 19;9:2109. doi: 10.3389/fimmu.2018.02109. eCollection 2018.
Tuberculosis (TB) is a global public health problem, which is caused by (Mtb). Type 2 diabetes mellitus (T2DM) is one of the leading predisposing factors for development of TB after HIV/AIDS. Glibenclamide is a widely used anti-diabetic drug in low and middle-income countries where the incidence of TB is very high. In a human macrophage cell line, glibenclamide, a KATP-channel blocker, promoted alternative activation of macrophages by enhancing expression of the M2 marker CD206 during M2 polarization. M2 macrophages are considered poorly microbicidal and associated with TB susceptibility. Here, we investigated the effect of glibenclamide on M1 and M2 phenotypes of primary human monocytes and further determined whether specific drug treatment for T2DM individuals influences the antibacterial function of monocytes in response to mycobacterial infection. We found that glibenclamide significantly reduced M1 (HLA-DR and CD86) surface markers and TNF-α production on primary human monocytes against mycobacterial infection. In contrast, M2 (CD163 and CD206) surface markers and IL-10 production were enhanced by pretreatment with glibenclamide. Additionally, reduction of bactericidal activity also occurred when primary human monocytes from T2DM individuals who were being treated with glibenclamide were infected with Mtb , consistent with the cytokine responses. We conclude that glibenclamide reduces M1 and promotes M2 polarization leading to impaired bactericidal ability of primary human monocytes of T2DM individuals in response to Mtb and may lead to increased susceptibility of T2DM individuals to TB and other bacterial infectious diseases.
肺结核（TB）是一个全球性的公共卫生问题，它是由结核分枝杆菌（Mtb）引起的。2 型糖尿病（T2DM）是继艾滋病（HIV/AIDS）之后导致结核病发展的主要易感因素之一。在中低收入国家，格列本脲是一种广泛使用的抗糖尿病药物，这些国家的结核病发病率非常高。在人类巨噬细胞系中，KATP 通道阻滞剂格列本脲通过在 M2 极化过程中增强 M2 标志物 CD206 的表达，促进巨噬细胞的替代激活。M2 巨噬细胞被认为杀菌能力差，与结核病易感性有关。在这里，我们研究了格列本脲对原代人单核细胞 M1 和 M2 表型的影响，并进一步确定了针对 T2DM 个体的特定药物治疗是否会影响单核细胞对分枝杆菌感染的抗菌功能。我们发现，格列本脲显著降低了原代人单核细胞针对分枝杆菌感染的 M1（HLA-DR 和 CD86）表面标志物和 TNF-α的产生。相比之下，格列本脲预处理增强了 M2（CD163 和 CD206）表面标志物和 IL-10 的产生。此外，当用格列本脲治疗的 T2DM 个体的原代人单核细胞感染 Mtb 时，杀菌活性也降低了，这与细胞因子反应一致。我们得出结论，格列本脲降低了 M1 并促进了 M2 的极化，导致 T2DM 个体原代人单核细胞对 Mtb 的杀菌能力受损，可能导致 T2DM 个体对结核病和其他细菌性传染病的易感性增加。
