Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, CA 91766-1854, USA.
Biomed Res Int. 2013;2013:402827. doi: 10.1155/2013/402827. Epub 2013 May 23.
Glutathione (GSH) is a tripeptide that regulates intracellular redox and other vital aspects of cellular functions. GSH plays a major role in enhancing the immune system. Dendritic cells (DCs) are potent antigen presenting cells that participate in both innate and acquired immune responses against microbial infections. Regulatory T cells (Tregs) play a significant role in immune homeostasis. In this study, we investigated the effects of GSH in enhancing the innate and adaptive immune functions of DCs against Mycobacterium tuberculosis (M. tb) infection. We also characterized the functions of the sub-populations of CD4+T cells such as Tregs and non-Tregs in modulating the ability of monocytes to control the intracellular M. tb infection. Our results indicate that GSH by its direct antimycobacterial activity inhibits the growth of intracellular M. tb inside DCs. GSH also increases the expressions of costimulatory molecules such as HLA-DR, CD80 and CD86 on the cell surface of DCs. Furthermore, GSH-enhanced DCs induced a higher level of T-cell proliferation. We also observed that enhancing the levels of GSH in Tregs resulted in downregulation in the levels of IL-10 and TGF- β and reduction in the fold growth of M. tb inside monocytes. Our studies demonstrate novel regulatory mechanisms that favor both innate and adaptive control of M. tb infection.
谷胱甘肽(GSH)是一种调节细胞内氧化还原和其他细胞功能重要方面的三肽。GSH 在增强免疫系统方面起着重要作用。树突状细胞(DCs)是一种强大的抗原呈递细胞,参与针对微生物感染的固有和获得性免疫反应。调节性 T 细胞(Tregs)在免疫稳态中起着重要作用。在这项研究中,我们研究了 GSH 增强树突状细胞对结核分枝杆菌(M. tb)感染的固有和适应性免疫功能的作用。我们还描述了 CD4+T 细胞亚群(如 Tregs 和非 Tregs)调节单核细胞控制细胞内 M. tb 感染能力的功能。我们的结果表明,GSH 通过其直接的抗分枝杆菌活性抑制细胞内 M. tb 在树突状细胞内的生长。GSH 还增加了 HLA-DR、CD80 和 CD86 等共刺激分子在树突状细胞表面的表达。此外,GSH 增强的树突状细胞诱导更高水平的 T 细胞增殖。我们还观察到,在 Tregs 中增强 GSH 水平会导致 IL-10 和 TGF-β水平下调,并减少单核细胞内 M. tb 的倍增。我们的研究表明了有利于控制 M. tb 感染的固有和适应性控制的新型调节机制。