Natural killer cells are recruited during pulmonary tuberculosis and their ex vivo responses to mycobacteria vary between healthy human donors in association with KIR haplotype.
Natural killer cells are recruited during pulmonary tuberculosis and their ex vivo responses to mycobacteria vary between healthy human donors in association with KIR haplotype.
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DOI：
10.1111/j.1462-5822.2012.01834.x
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发表时间：
2012-11
影响因子：
3.4
通讯作者：
Young D
中科院分区：
文献类型：
--
作者：
Portevin D;Via LE;Eum S;Young D
人类对结核病的易感性差异很大。虽然只有少数人会发展为疾病，但大多数暴露于结核分枝杆菌的健康个体会产生免疫反应，可以清除或抑制静止形式的感染。使用免疫荧光对人类临床样本，我们确定了自然杀伤（NK）细胞浸润肉芽肿性肺病变活动性疾病。为了比较NK细胞在结核感染和牛分枝杆菌BCG疫苗接种的情况下对游离分枝杆菌的反应能力，从匿名健康人供体的外周血中分离NK细胞，并用M.结核杆菌H37 Rv或M.牛卡介苗胞外M.结核和M.在IL-2存在下，BCG同样可以触发NK细胞释放IFNγ和TNFα。然而，我们发现这种反应在个体之间变化1000倍（n = 52），KIR单倍型的差异提供了区分低应答者和高应答者的重要标准。我们的研究结果表明，KIR基因座的变化以及NK细胞库的变化可能会影响对分枝杆菌的细胞因子产生，我们认为这种先天性的变异性可以维持对分枝杆菌不同水平的易感性。肺结核感染。
Humans vary widely in their susceptibility to tuberculosis. While only a minority will progress to disease, the majority of healthy individuals exposed to Mycobacterium tuberculosis mount an immune response that can clear or contain the infection in a quiescent form. Using immunofluorescence on human clinical samples, we identified natural killer (NK) cells infiltrating granulomatous pulmonary lesions during active disease. In order to compare the NK cell ability to react to free mycobacteria in the context of tuberculosis infection and Mycobacterium bovis BCG vaccination, NK cells were isolated from the peripheral blood of anonymous healthy human donors, and stimulated with M. tuberculosis H37Rv or M. bovis BCG. Extracellular M. tuberculosis and M. bovis BCG could equally trigger the release of IFNγ and TNFα from NK cells in the presence of IL-2. However, we found that this response varied 1000-fold between individuals (n = 52), with differences in KIR haplotype providing a significant criterion to distinguish between low and high responders. Our findings suggest that variations at the KIR locus and therefore of the NK cell repertoire may affect cytokine production in response to mycobacteria and we propose that this innate variability couldsustain different levels of susceptibility to M. tuberculosis infection.
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DOI：
10.4049/jimmunol.0804224
发表时间：
2009-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Korbel DS;Norman PJ;Newman KC;Horowitz A;Gendzekhadze K;Parham P;Riley EM
通讯作者：
Riley EM
DOI：
10.4049/jimmunol.1001951
发表时间：
2010-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Moesta AK;Graef T;Abi-Rached L;Older Aguilar AM;Guethlein LA;Parham P
通讯作者：
Parham P
影响因子：
--
作者：
Marras F;Bozzano F;De Maria A
通讯作者：
De Maria A
影响因子：
--
作者：
Leung, Wai Lin;Law, Kai Leung;Kam, Kai Man
通讯作者：
Kam, Kai Man
影响因子：
4.4
作者：
Marcenaro, Emanuela;Ferranti, Bruna;Moretta, Alessandro
通讯作者：
Moretta, Alessandro