Altered monocyte phenotypes but not impaired peripheral T cell immunity may explain susceptibility of the elderly to develop tuberculosis.
Altered monocyte phenotypes but not impaired peripheral T cell immunity may explain susceptibility of the elderly to develop tuberculosis.
复制标题
单核细胞表型的改变，但不会受损的外周T细胞免疫力可以解释老年人对发展结核病的敏感性。
DOI：
10.1016/j.exger.2018.06.029
复制
发表时间：
2018-10-01
影响因子：
3.9
通讯作者：
Turner J
中科院分区：
文献类型：
--
作者：
Ault R;Dwivedi V;Koivisto E;Nagy J;Miller K;Nagendran K;Chalana I;Pan X;Wang SH;Turner J
结核病（TB）是全球范围内的主要杀手，是一种单一的传染病。随着全球人口老龄化，老年人结核病的发病率和死亡率最高。虽然与老年相关的一般免疫衰老被认为有助于老年人发展为活动性TB疾病的易感性，但很少有对患有结核分枝杆菌（M.tb）感染或疾病的老年个体的免疫功能进行研究。特别是，对结核分枝杆菌的适应性T细胞免疫力受损是老年人易感性增加的一种拟议机制，主要是基于老年人皮肤中对结核菌素纯化蛋白衍生物的迟发型超敏反应下降。为了研究老年人易患活动性结核病的免疫学原因，我们进行了一项为期五年（2012-2016年）的横断面观察性研究，招募了来自2个年龄组（成人：25-44岁;老年人：65岁及以上）和3种结核分枝杆菌感染状态（活动性结核、潜伏性结核感染和无结核分枝杆菌感染史的健康对照）的参与者。我们假设外周T细胞免疫功能受损在老年人对结核病的生物易感性中起作用。与我们的假设相反，我们没有观察到老年人外周血中结核分枝杆菌特异性T细胞频率受损或结核分枝杆菌控制中涉及的细胞因子（IFN-γ，IL-10）产生改变的证据。相反，我们观察到单核细胞比例和表型随年龄和结核分枝杆菌感染的变化，表明它们在老年人发展为活动性结核病的易感性中的潜在作用。我们的研究结果表明，老年人广泛存在的低度全身性炎症（称为“炎症”）与老年人对活动性结核病的特异性易感性之间存在潜在联系。此外，我们的研究结果强调需要进一步研究老年人更容易患结核病和死于结核病的生物学原因，以便公共卫生系统能够更好地应对全球人口老龄化中当前和未来的结核病问题。
Tuberculosis (TB) is the leading killer due to a single infectious disease worldwide. With the aging of the global population, the case rate and deaths due to TB are highest in the elderly population. While general immunosenescence associated with old age is thought to contribute to the susceptibility of the elderly to develop active TB disease, very few studies of immune function in elderly individuals with Mycobacterium tuberculosis (M.tb) infection or disease have been performed. In particular, impaired adaptive T cell immunity to M.tb is one proposed mechanism for the elderly’s increased susceptibility primarily on the basis of the decreased delayed type hypersensitivity response to tuberculin-purified protein derivative in the skin of elderly individuals. To investigate immunological reasons why the elderly are susceptible to develop active TB disease, we performed a cross-sectional observational study over a five year period (2012–2016) enrolling participants from 2 age groups (adults: 25–44 years; elderly: 65 and older) and 3 M.tb infection statuses (active TB, latent TB infection, and healthy controls without history of M.tb infection). We hypothesized that impaired peripheral T cell immunity plays a role in the biological susceptibility of the elderly to TB. Contrary to our hypothesis, we observed no evidence of impaired M.tb specific T cell frequency or altered production of cytokines implicated in M.tb control (IFN-γ, IL-10) in peripheral blood in the elderly. Instead, we observed alterations in monocyte proportion and phenotype with age and M.tb infection that suggest their potential role in the susceptibility of the elderly to develop active TB. Our results suggest a potential link between the known widespread low-grade systemic inflammation of old age, termed “inflammaging,” with the elderly’s specific susceptibility to developing active TB. Moreover, our results highlight the need for further research into the biological reasons why the elderly are more susceptible to disease and death from TB, so that public health systems can be better equipped to face the present and future problem of TB in an aging global population.
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DOI：
10.1084/jem.20090896
发表时间：
2009-08-31
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Agius E;Lacy KE;Vukmanovic-Stejic M;Jagger AL;Papageorgiou AP;Hall S;Reed JR;Curnow SJ;Fuentes-Duculan J;Buckley CD;Salmon M;Taams LS;Krueger J;Greenwood J;Klein N;Rustin MH;Akbar AN
通讯作者：
Akbar AN
DOI：
10.4049/jimmunol.181.8.5545
发表时间：
2008-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Beamer GL;Flaherty DK;Assogba BD;Stromberg P;Gonzalez-Juarrero M;de Waal Malefyt R;Vesosky B;Turner J
通讯作者：
Turner J
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.1
作者：
Bonecini-Almeida, MG;Ho, JL;Silva, JRLE
通讯作者：
Silva, JRLE
影响因子：
3.5
作者：
CASTLE, SC;NORMAN, DC;MAKINODAN, T
通讯作者：
MAKINODAN, T