IFN-γ independent markers of Mycobacterium tuberculosis exposure among male South African gold miners.
IFN-γ independent markers of Mycobacterium tuberculosis exposure among male South African gold miners.
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DOI：
10.1016/j.ebiom.2023.104678
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发表时间：
2023-07
期刊：
影响因子：
11.1
通讯作者：
Seshadri, Chetan
中科院分区：
文献类型：
--
作者：
Davies, Leela R. L.;Smith, Malisa T.;Cizmeci, Deniz;Fischinger, Stephanie;Lee, Jessica Shih-Lu;Lu, Lenette L.;Layton, Erik D.;Grant, Alison D.;Fielding, Katherine;Stein, Catherine M.;Boom, W. Henry;Hawn, Thomas R.;Fortune, Sarah M.;Wallis, Robert S.;Churchyard, Gavin J.;Alter, Galit;Seshadri, Chetan
南非金矿工人的结核病患病率是世界上最高的，但一小部分矿工在结核菌素皮肤试验（TST）和IFN-γ释放试验（IGRA）中始终显示阴性结果。我们假设这些“抵抗者”（rstr）可能表现出暴露于结核分枝杆菌（M.tb）的非常规免疫特征。在一组潜伏性结核感染（LTBI）的rstr和匹配对照中，我们分别使用多参数流式细胞术和系统血清学分析了结核分枝杆菌抗原特异性T细胞和抗体反应的功能广度。rstr和LTBI对照均表现出对结核分枝杆菌特异性抗原ESAT-6和CFP-10不依赖IFN-γ的t细胞和IgG抗体反应。抗原特异性抗体Fc半乳糖基化和唾液酰化在rstr中较高。在联合T细胞和抗体分析中，结核分枝杆菌裂解物刺激T细胞分泌TNF与纯化蛋白衍生物特异性IgG水平呈正相关。综合数据的多变量模型能够区分RSTR和LTBI受试者。暴露于结核分枝杆菌的IFN-γ不依赖免疫特征，未被批准的临床诊断检测到，在具有强烈和长期感染压力的独特特征的职业队列中很容易检测到。此外，TNF可能介导结核分枝杆菌特异性t细胞和b细胞之间的协调反应。这项工作得到了（R01-AI124348给Boom、Stein和Hawn； R01-AI125189和R01-AI146072给Seshadri； 75N93019C00071给Fortune、Alter、Seshadri和Boom）、（Davies）、（OPP1151836和OPP1109001给Hawn；和OPP1151840给Alter）、（Fortune）和（Fortune）的支持。
The prevalence of tuberculosis among men who work in the gold mines of South Africa is among the highest in the world, but a fraction of miners demonstrate consistently negative results upon tuberculin skin test (TST) and IFN-γ release assay (IGRA). We hypothesized that these “resisters” (RSTRs) may display unconventional immune signatures of exposure to M. tuberculosis (M.tb). In a cohort of RSTRs and matched controls with latent TB infection (LTBI), we profiled the functional breadth of M.tb antigen-specific T cell and antibody responses using multi-parameter flow cytometry and systems serology, respectively. RSTRs and LTBI controls both exhibited IFN-γ independent T-cell and IgG antibody responses to M.tb-specific antigens ESAT-6 and CFP-10. Antigen-specific antibody Fc galactosylation and sialylation were higher among RSTRs. In a combined T-cell and antibody analysis, M.tb lysate-stimulated TNF secretion by T cells correlated positively with levels of purified protein derivative-specific IgG. A multivariate model of the combined data was able to differentiate RSTR and LTBI subjects. IFN-γ independent immune signatures of exposure to M.tb, which are not detected by approved clinical diagnostics, are readily detectable in an occupational cohort uniquely characterized by intense and long-term infection pressure. Further, TNF may mediate a coordinated response between M.tb-specific T-cells and B-cells. This work was supported by the (R01-AI124348 to Boom, Stein, and Hawn; R01-AI125189 and R01-AI146072 to Seshadri; and 75N93019C00071 to Fortune, Alter, Seshadri, and Boom), the (Davies), the (OPP1151836 and OPP1109001 to Hawn; and OPP1151840 to Alter), (Fortune), and (Fortune).
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影响因子：
4.3
作者：
Finak G;Frelinger J;Jiang W;Newell EW;Ramey J;Davis MM;Kalams SA;De Rosa SC;Gottardo R
通讯作者：
Gottardo R
影响因子：
3.7
作者：
Chihota VN;Ntshiqa T;Maenetje P;Mansukhani R;Velen K;Hawn TR;Wallis R;Grant AD;Churchyard GJ;Fielding K
通讯作者：
Fielding K
影响因子：
7.3
作者：
Gutierrez J;Kroon EE;Möller M;Stein CM
通讯作者：
Stein CM
影响因子：
158.5
作者：
Churchyard, Gavin J.;Fielding, Katherine L.;Grant, Alison D.
通讯作者：
Grant, Alison D.
DOI：
10.1073/pnas.1611776114
发表时间：
2017-05-09
影响因子：
11.1
作者：
Li, Hao;Wang, Xing-xing;Javid, Babak
通讯作者：
Javid, Babak