DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
South African Tuberculosis Vaccine Initiative, Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Front Immunol. 2022 Mar 8;13:839747. doi: 10.3389/fimmu.2022.839747. eCollection 2022.
Myeloid-derived suppressor cells (MDSC) have been identified in the peripheral blood and granulomas of patients with active TB disease, but their phenotype-, function-, and immunosuppressive mechanism- spectrum remains unclear. Importantly, the frequency and signaling pathways of MDSC at the site of disease is unknown with no indication how this compares to MDSC identified in peripheral blood or to those of related myeloid counterparts such as alveolar macrophages and monocytes. Most phenotypic and functional markers have been described in oncological studies but have not yet been validated in TB. Using a panel of 43 genes selected from pathways previously shown to contribute to tumor-derived MDSC, we set out to evaluate if the expression of these additional functional markers and properties may also be relevant to TB-derived MDSC. Differential expression was investigated between MDSC, alveolar macrophages and monocytes enriched from bronchoalveolar lavage fluid and peripheral blood of patients with active TB, patients with other lung diseases (OLD). Results demonstrated that anatomical compartments may drive compartment-specific immunological responses and subsequent MDSC immunosuppressive functions, demonstrated by the observation that MDSC and/or monocytes from PB alone can discriminate, hierarchical clustering, between patients with active TB disease and OLD. Our data show that the gene expression patterns of MDSC in peripheral blood and bronchoalveolar lavage fluid do not cluster according to disease states (TB vs OLD). This suggests that MDSC from TB patients may display similar gene expression profiles to those found for MDSC in cancer, but this needs to be validated in a larger cohort. These are important observations for TB research and may provide direction for future studies aimed at repurposing and validating cancer immunotherapies for use in TB.
髓系来源的抑制细胞（MDSC）已在活动性结核病患者的外周血和肉芽肿中被鉴定出来，但它们的表型、功能和免疫抑制机制范围尚不清楚。重要的是，疾病部位的 MDSC 的频率和信号通路尚不清楚，也没有迹象表明其与外周血中鉴定的 MDSC 或与肺泡巨噬细胞和单核细胞等相关髓样细胞相比如何。大多数表型和功能标志物已在肿瘤学研究中描述，但尚未在结核病中得到验证。我们使用了一组从先前显示有助于肿瘤衍生 MDSC 的途径中选择的 43 个基因，旨在评估这些额外的功能标志物和特性的表达是否也与结核病衍生的 MDSC 相关。我们研究了来自活动性结核病患者、其他肺部疾病（OLD）患者支气管肺泡灌洗液和外周血中分离的 MDSC、肺泡巨噬细胞和单核细胞之间这些基因的差异表达。结果表明，解剖隔室可能驱动特定隔室的免疫反应和随后的 MDSC 免疫抑制功能，这一观察结果表明，仅来自 PB 的 MDSC 和/或单核细胞可以区分活动性结核病患者和 OLD 患者，进行层次聚类。我们的数据表明，外周血和支气管肺泡灌洗液中 MDSC 的基因表达模式不根据疾病状态（TB 与 OLD）聚类。这表明 TB 患者的 MDSC 可能表现出与癌症中发现的 MDSC 相似的基因表达谱，但这需要在更大的队列中进行验证。这些对于结核病研究是重要的观察结果，并可能为旨在重新利用和验证癌症免疫疗法用于结核病的未来研究提供方向。
