Previous studies have suggested that isolates of Mycobacterium tuberculosis responsible for tuberculosis outbreaks grow more rapidly within human mononuclear phagocytes than do other isolates. Clinical scenarios suggesting virulence of specific M. tuberculosis isolates are readily identified. Determination of appropriate "control" isolates for these studies is more problematic, but equally important for validating these assays and, ultimately, for identifying biologic differences between M. tuberculosis strains that contribute to virulence. We utilized the database from a study of Ugandan tuberculosis patients and their household (HH) contacts to identify M. tuberculosis isolates transmitted within HH and nontransmitted control isolates. Isolate pairs were evaluated from matched HH in each of three clinical scenarios: (i) coprevalent disease and no disease, (ii) incident disease and no disease, and (iii) M. tuberculosis infection (purified protein derivative [PPD] positive) and no infection (PPD negative). Intracellular growth of paired organisms was determined in a blinded fashion using two models of intracellular infection in which we have previously demonstrated correlation between intracellular growth and strain virulence, primary human monocytes (MN) and THP-1 human macrophage-like cells. In both models, transmitted isolates from coprevalent disease HH displayed more rapid growth than nontransmitted control isolates. In the THP-1 model, this was also true of transmitted isolates from HH with incident disease and their controls. Differences in production of tumor necrosis factor alpha and interleukin-10 by matched isolates showed correlation with growth patterns in the THP-1 cells but not in MN. Paired isolates characterized in this manner may be of particular interest for further investigations of the virulence of M. tuberculosis.

译文

先前的研究表明,负责结核病暴发的结核分枝杆菌分离株在人类单核吞噬细胞内的生长速度比其他分离株更快。提示特定结核分枝杆菌分离株毒力的临床情景很容易确定。为这些研究确定适当的 “对照” 分离株是更成问题的,但对于验证这些测定以及最终确定有助于毒力的结核分枝杆菌菌株之间的生物学差异同样重要。我们利用乌干达结核病患者及其家庭 (HH) 接触者的研究数据库来确定在HH内传播的结核分枝杆菌分离株和非传播的对照分离株。在三种临床情况下,从匹配的HH评估分离对 :( i) 共价疾病和无疾病,(ii) 突发疾病和无疾病,以及 (iii) 结核分枝杆菌感染 (纯化的蛋白衍生物 [PPD] 阳性) 和无感染 (PPD阴性)。使用两种细胞内感染模型以盲方式确定配对生物的细胞内生长,其中我们先前已经证明了细胞内生长与菌株毒力,原代人单核细胞 (MN) 和THP-1人巨噬细胞样细胞之间的相关性。在这两个模型中,来自共价疾病HH的传播分离株比未传播的对照分离株显示出更快的生长。在THP-1模型中,具有突发疾病的HH传播分离株及其对照也是如此。匹配的分离株在肿瘤坏死因子 α 和interleukin-10产生方面的差异显示出与THP-1细胞中的生长模式相关,而与MN中的生长模式无关。以这种方式表征的成对分离株对于进一步研究结核分枝杆菌的毒力可能特别感兴趣。

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