Neutrophils Contribute to Severity of Tuberculosis Pathology and Recovery From Lung Damage Pre- and Posttreatment.
Neutrophils Contribute to Severity of Tuberculosis Pathology and Recovery From Lung Damage Pre- and Posttreatment.
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DOI：
10.1093/cid/ciab729
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发表时间：
2022-05-30
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影响因子：
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尽管有微生物治疗，但约50%的结核病患者肺部恢复不良。中性粒细胞与肺部病理有关；然而，CD16/ cd62l定义的亚群尚未在结核病中得到研究。利用流式细胞术，我们监测了结核分枝杆菌（Mtb）全细胞裂解液（WCL）和ESAT-6/CFP-10融合蛋白（EC）刺激后中性粒细胞的频率、表型和功能与肺病理的关系。分析了42例成人人类免疫缺陷病毒（HIV）阴性结核病患者治疗前后的新鲜血液，并通过胸片和细菌负荷确定疾病严重程度。流式细胞术用于监测mmb特异性抗原刺激2小时后中性粒细胞的频率、表型和功能（活性氧[ROS]的产生，以及CD11b、肿瘤坏死因子和白细胞介素10 [IL-10]的表达）。与基线相比，治疗后总中性粒细胞减少（P = 0.0059）；CD16brCD62Lbr（节段性）中性粒细胞增加（P = 0.0031）， CD16dimCD62Lbr（带状）中性粒细胞减少（P = 0.038）。在基线时，严重肺损伤患者的带状中性粒细胞较低（P = 0.035）。在WCL刺激后，即使在性别调整后，低Mtb负荷患者的节段性中性粒细胞ROS也更高(P =。在基线时，表达il -10的CD16dimCD62Llo细胞在轻度损伤患者中更高（P = 0.0397）。高ROS生成、低水平带状中性粒细胞和高水平表达il -10的CD16dimCD62Llo中性粒细胞与诊断时肺部病理减少有关。因此，中性粒细胞是结核病严重程度的潜在早期指标，也是结核病宿主定向治疗的有希望的靶点。中性粒细胞介导的（功能性保护亚型和活性氧生成能力的比例）结核病易感性为未来针对结核病进展和严重程度的免疫抑制宿主导向疗法的机制和临床研究提供了强有力的科学前提。
Despite microbiological cure, about 50% of tuberculosis (TB) patients have poor lung recovery. Neutrophils are associated with lung pathology; however, CD16/CD62L-defined subsets have not been studied in TB. Using flow cytometry, we monitored frequencies, phenotype, and function of neutrophils following stimulation with Mycobacterium tuberculosis (Mtb) whole cell lysate (WCL) and ESAT-6/CFP-10 fusion protein (EC) in relation to lung pathology. Fresh blood from 42 adult, human immunodeficiency virus (HIV)–negative TB patients were analyzed pre- and post-therapy, with disease severity determined using chest radiography and bacterial load. Flow cytometry was used to monitor frequencies, phenotype, and function (generation of reactive oxygen species [ROS], together with CD11b, tumor necrosis factor, and interleukin 10 [IL-10] expression) of neutrophils following 2-hour stimulation with Mtb-specific antigens. Total neutrophils decreased by post-treatment compared to baseline (P = .0059); however, CD16brCD62Lbr (segmented) neutrophils increased (P = .0031) and CD16dimCD62Lbr (banded) neutrophils decreased (P = .038). Banded neutrophils were lower in patients with severe lung damage at baseline (P = .035). Following WCL stimulation, ROS from segmented neutrophils was higher in patients with low Mtb loads even after adjusting for sex (P = .038), whereas IL-10–expressing CD16dimCD62Llo cells were higher in patients with mild damage (P = .0397) at baseline. High ROS generation, low levels of banded neutrophils, and high levels of IL-10–expressing CD16dimCD62Llo neutrophils are associated with reduced lung pathology at diagnosis. Hence, neutrophils are potential early indicators of TB severity and promising targets for TB host-directed therapy. Neutrophil-mediated (proportions of functional protective subtypes and reactive oxygen species generation capacity) tuberculosis susceptibility constitutes a strong scientific premise for future mechanistic and clinical studies targeting immunosuppressive host-directed therapies for tuberculosis disease progression and severity.
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影响因子：
10
作者：
Ralph, Anna P.;Ardian, Muhamed;Kelly, Paul M.
通讯作者：
Kelly, Paul M.
DOI：
10.1590/s1806-37562016000000053
发表时间：
2017-01
期刊：
Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia
影响因子：
--
作者：
Chushkin MI;Ots ON
通讯作者：
Ots ON
影响因子：
4
作者：
Rosales C
通讯作者：
Rosales C
影响因子：
4.6
作者：
Lyadova IV
通讯作者：
Lyadova IV
影响因子：
81.5
作者：
Pai, Madhukar;Behr, Marcel A.;Raviglione, Mario
通讯作者：
Raviglione, Mario