Increased Frequency of Myeloid-derived Suppressor Cells during Active Tuberculosis and after Recent Mycobacterium tuberculosis Infection Suppresses T-Cell Function
Increased Frequency of Myeloid-derived Suppressor Cells during Active Tuberculosis and after Recent Mycobacterium tuberculosis Infection Suppresses T-Cell Function
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DOI：
10.1164/rccm.201302-0249oc
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发表时间：
2013-09-15
影响因子：
24.7
通讯作者：
Walzl, Gerhard
中科院分区：
文献类型：
--
作者：
du Plessis, Nelita;Loebenberg, Laurianne;Walzl, Gerhard
理由：T细胞应答不足可能导致结核病（TB）的发展。骨髓源性抑制细胞（MDSC）在肿瘤生物学和最近的几种感染性疾病中被描述为T细胞功能的抑制因子。目的：探讨MDSC在TB中的存在和作用。我们分析了结核病和肺癌患者外周血和疾病部位MDSC的表面标志物，以及近期（家庭）或远程暴露于结核分枝杆菌（M.tb）的无症状结核菌素皮肤试验阳性个体和未感染的健康对照受试者的外周血中。为了评估MDSCs的抑制能力，分离了感染结核分枝杆菌和结核病例的家庭接触者的细胞，并与CD 3（+）T细胞共培养。测量和主要结果：我们的研究结果表明，在最近的结核分枝杆菌感染和疾病后，MDSCs的存在增加。我们证实它们抑制CD 4（+）T细胞功能，包括减少细胞因子反应和抑制CD 4（+）T细胞增殖。只有来自TB病例的MDSC减少了T细胞活化，改变了T细胞运输，并抑制了CD 8（+）T细胞功能。结核分枝杆菌扩增的MDSC与显著更高的IL-1b、IL-6、IL-8、粒细胞集落刺激因子和单核细胞趋化蛋白-1相关，并且在共培养中降低粒细胞-巨噬细胞集落刺激因子和巨噬细胞炎性蛋白-1 β水平。这些数据表明，先天MDSC不仅在活动性TB期间以与癌症中发现的相似水平被诱导，而且在最近暴露于结核分枝杆菌的健康个体中也是如此。这些细胞减少了保护性T细胞反应，可能导致宿主无法根除感染，并增加了结核病的后续发展。
Rationale: Inadequacy of T-cell responses may result in the development of tuberculosis (TB). Myeloid-derived suppressor cells (MDSCs) have been described as suppressors of T-cell function in cancer biology and recently in several infectious diseases.Objectives: To explore the presence and role of MDSCs in TB.Methods: We analyzed surface markers of MDSCs in peripheral blood and at the site of disease in TB cases and in patients with lung cancer, and in peripheral blood of asymptomatic tuberculin skin test-positive individuals with recent (household) or remote exposure to Mycobacterium tuberculosis (M.tb) and in uninfected healthy control subjects. To evaluate the suppressive capacity of MDSCs, cells of household contacts infected with M.tb and TB cases were isolated and cocultured with CD3(+) T cells.Measurements and Main Results: Our results demonstrate an increased presence of MDSCs after recent M.tb infection and disease. We confirm their suppression of CD4(+) T-cell function, including reduced cytokine responses and inhibition of CD4(+) T-cell proliferation. Only MDSCs from TB cases reduced T-cell activation, altered T-cell trafficking, and suppressed CD8(+) T-cell functions. M.tb-expanded MDSCs were associated with significantly higher IL-1b, IL-6, IL-8, granulocyte colony-stimulating factor, and monocyte chemotactic protein-1, and reduced granulocyte-macrophage colony-stimulating factor and macrophage inflammatory protein-1 beta levels in coculture.Conclusions: These data reveal that innate MDSCs are induced not only during active TB at similar levels as found in cancer, but also in healthy individuals after recent exposure to M.tb. These cells diminish protective T-cell responses and may contribute to the inability of hosts to eradicate the infection and add to the subsequent development of TB disease.