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首页> 外文期刊>Clinical and vaccine immunology: CVI >Abnormal Immune Responses in Persons with Previous Extrapulmonary Tuberculosis in an In Vitro Model That Simulates In Vivo Infection with Mycobacterium tuberculosis
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Abnormal Immune Responses in Persons with Previous Extrapulmonary Tuberculosis in an In Vitro Model That Simulates In Vivo Infection with Mycobacterium tuberculosis

机译：模拟结核分枝杆菌体内感染的体外模型中先前肺外结核患者的免疫反应异常

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Persons with previous extrapulmonary tuberculosis have reduced peripheral blood mononuclear cell cytokine production and CD4+ lymphocytes compared to persons with previous pulmonary tuberculosis or latent tuberculosis infection, but specific defects related to Mycobacterium tuberculosis infection of macrophages have not been characterized. The objective of this study was to further characterize the in vitro immune responses to M. tuberculosis infection in HIV-seronegative persons with previous extrapulmonary tuberculosis. Peripheral blood mononuclear cells were isolated from HIV-seronegative persons with previous extrapulmonary tuberculosis (n = 11), previous pulmonary tuberculosis (n = 21), latent M. tuberculosis infection (n = 19), and uninfected tuberculosis contacts (n = 20). Experimental conditions included M. tuberculosis-infected macrophages cultured with and without monocyte-depleted peripheral blood mononuclear cells. Concentrations of interleukin 1β (IL-1β), IL-4, IL-6, CXCL8 (IL-8), IL-10, IL-12p70, IL-17, CCL2 (monocyte chemoattractant protein 1), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) were measured by multiplex cytokine array. When M. tuberculosis-infected macrophages were cocultured with monocyte-depleted peripheral blood mononuclear cells, IFN-γ (P = 0.01), TNF-α (P = 0.04), IL-10 (P < 0.001), and IL-6 (P = 0.03) exhibited similar continua of responses, with uninfected persons producing the lowest levels, followed by extrapulmonary tuberculosis cases, pulmonary tuberculosis controls, and persons with latent M. tuberculosis infection. A similar pattern was observed with CXCL8 (P = 0.04), IL-10 (P = 0.02), and CCL2 (P = 0.03) when monocyte-depleted peripheral blood mononuclear cells from the four groups were cultured alone. Persons with previous extrapulmonary tuberculosis had decreased production of several cytokines, both at rest and after stimulation with M. tuberculosis. Our results suggest that persons who develop extrapulmonary tuberculosis have a subtle global immune defect that affects their response to M. tuberculosis infection.
机译：与先前肺结核或潜伏性结核感染者相比，先前肺外结核患者的外周血单核细胞细胞因子产生和CD4 + 淋巴细胞减少，但尚未鉴定与巨噬细胞结核分枝杆菌感染有关的特定缺陷。这项研究的目的是进一步表征先前患有肺外结核的HIV阴性人群对结核分枝杆菌感染的体外免疫反应。从先前有肺外结核（ n = 11），先前有肺结核（ n = 21），潜伏性结核分枝杆菌感染（HIV）的HIV阴性人群中分离外周血单个核细胞 n = 19）和未感染的结核病接触者（ n = 20）。实验条件包括用和不用单核细胞耗尽的外周血单核细胞培养的结核分枝杆菌感染的巨噬细胞。白细胞介素1β（IL-1β），IL-4，IL-6，CXCL8（IL-8），IL-10，IL-12p70，IL-17，CCL2（单核细胞趋化蛋白1），肿瘤坏死因子α（通过多重细胞因子阵列测量TNF-α和γ-干扰素（IFN-γ）。当结核分枝杆菌感染的巨噬细胞与单核细胞耗尽的外周血单核细胞共培养时，IFN-γ（ P = 0.01），TNF-α（ P = 0.04）， IL-10（ P <0.001）和IL-6（ P = 0.03）表现出相似的连续性，未感染者水平最低，其次是肺外结核病例，肺结核控制者以及潜在的结核分枝杆菌感染者。 CXCL8（ P = 0.04），IL-10（ P = 0.02）和CCL2（ P = 0.03）观察到类似的模式当单独培养来自四组的单核细胞耗尽的外周血单核细胞时。先前患有肺外结核病的人，在静止和结核分枝杆菌刺激后，几种细胞因子的产量均下降。我们的结果表明，发生肺外结核的人具有微妙的整体免疫缺陷，影响了他们对结核分枝杆菌感染的反应。

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