IFNG-mediated immune responses enhance autophagy against <i>Mycobacterium tuberculosis</i> antigens in patients with active tuberculosis

Protective immunity against <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) requires IFNG. Besides, IFNG-mediated induction of autophagy suppresses survival of virulent <i>Mtb</i> in macrophage cell lines. We investigated the contribution of autophagy to the defense against <i>Mtb</i> antigen (<i>Mtb</i>-Ag) in cells from tuberculosis patients and healthy donors (HD). Patients were classified as high responders (HR) if their T cells produced significant IFNG against <i>Mtb</i>-Ag; and low responders (LR) when patients showed weak or no T cell responses to <i>Mtb</i>-Ag. The highest autophagy levels were detected in HD cells whereas the lowest quantities were observed in LR patients. Interestingly, upon <i>Mtb-</i>Ag stimulation, we detected a positive correlation between IFNG and MAP1LC3B-II –II /LC3-II levels. Actually, blockage of <i>Mtb</i>-Ag-induced IFNG markedly reduced autophagy in HR patients whereas addition of limited amounts of IFNG significantly increased autophagy in LR patients. Therefore, autophagy collaborates with human immune responses against <i>Mtb</i> in close association with specific IFNG secreted against the pathogen.抗结核分枝杆菌（Mycobacterium tuberculosis, Mtb）的保护性免疫依赖于干扰素γ（IFNG）。此外，IFNG介导的自噬诱导可抑制致病性结核分枝杆菌在巨噬细胞系中的存活。本研究探究了自噬对结核患者与健康捐献者（HD）细胞中抗结核分枝杆菌抗原（Mtb-Ag）防御反应的贡献。研究将患者分为两类：若其T细胞针对Mtb-Ag产生显著水平的IFNG，则归类为高反应者（HR）；若患者T细胞对Mtb-Ag应答微弱或无应答，则归类为低反应者（LR）。实验检测发现，健康捐献者细胞的自噬水平最高，而LR患者细胞的自噬水平最低。值得注意的是，经Mtb-Ag刺激后，IFNG与MAP1LC3B-II（LC3-II）水平呈正相关。具体而言，阻断Mtb-Ag诱导产生的IFNG可显著降低HR患者细胞的自噬水平，而添加少量IFNG则可显著提升LR患者细胞的自噬水平。综上，自噬可与人类抗Mtb免疫应答协同发挥作用，且与针对该病原体分泌的特异性IFNG密切相关。

搜集汇总

背景与挑战

背景概述

该数据集研究了IFN-γ介导的免疫反应在活动性结核病患者中增强对结核分枝杆菌抗原的自噬作用。研究发现，自噬水平在健康捐赠者中最高，在低反应患者中最低，且IFN-γ与自噬标志物MAP1LC3B-II呈正相关，表明自噬与针对结核分枝杆菌的免疫防御密切相关。数据集属于免疫学和微生物学领域，重点关注自噬、T细胞反应和结核病免疫机制。