Laboratory of Immunopharmacology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico City 14080, Mexico.
Department of Microbiology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico City 14080, Mexico.
Biomolecules. 2021 Nov 25;11(12):1763. doi: 10.3390/biom11121763.
Type 2 diabetes is an established risk factor for tuberculosis, but the underlying mechanisms are largely unknown. We established an in vitro model to analyze the effect of high glucose concentrations in antigen processing and presentation in antigen-presenting cells. Human monocyte-derived macrophages (MDMs) were exposed to high (11 mM and 30 mM) and low (5.5 mM) glucose concentrations and infected with . Flow cytometry was used to analyze the effect of high glucose concentrations in histocompatibility complex (MHC) class II molecules (HLA-DR) and co-stimulatory molecules (CD80 and CD86), indispensable for an adequate antigenic presentation and CD4+ T cell activation. HLA-DR and CD86 were significantly decreased by high glucose concentrations compared with low glucose concentrations. Confocal microscopy was used to detect Rab 5 and Lamp-1, proteins involved in the kinetics of antigen processing as early markers, and Rab 7 and cathepsin D as late markers. We observed a delay in the dynamics of the acquisition of Rab 7 and cathepsin D in high glucose concentrations. Moreover, the kinetics of the formation peptide-MHC II complexes in MDMs was decreased under high glucose concentrations, reducing their capacity for T cell activation. These findings suggest that high glucose concentrations directly affect antigenic processing, and therefore antigenic presentation.
2 型糖尿病是结核病的一个既定危险因素，但潜在机制在很大程度上尚不清楚。我们建立了体外模型来分析高葡萄糖浓度对抗原呈递细胞中抗原加工和呈递的影响。用人单核细胞衍生的巨噬细胞（MDM）暴露于高（11mM 和 30mM）和低（5.5mM）葡萄糖浓度，并感染 。流式细胞术用于分析高葡萄糖浓度对半相合复合物（MHC）II 类分子（HLA-DR）和共刺激分子（CD80 和 CD86）的影响，这些分子对于适当的抗原呈递和 CD4+T 细胞激活是必不可少的。与低葡萄糖浓度相比，高葡萄糖浓度显著降低了 HLA-DR 和 CD86 的表达。共聚焦显微镜用于检测 Rab5 和 Lamp-1，这些蛋白作为早期标志物参与抗原加工动力学，以及 Rab7 和组织蛋白酶 D 作为晚期标志物。我们观察到 Rab7 和组织蛋白酶 D 在高葡萄糖浓度下的获得动力学延迟。此外，高葡萄糖浓度下 MDM 中肽-MHC II 复合物形成的动力学降低，降低了它们激活 T 细胞的能力。这些发现表明，高葡萄糖浓度直接影响抗原加工，从而影响抗原呈递。
