Human macrophage responses to clinical isolates from the Mycobacterium tuberculosis complex discriminate between ancient and modern lineages.
Human macrophage responses to clinical isolates from the Mycobacterium tuberculosis complex discriminate between ancient and modern lineages.
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DOI：
10.1371/journal.ppat.1001307
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发表时间：
2011-03
期刊：
影响因子：
6.7
通讯作者：
Young D
中科院分区：
文献类型：
--
作者：
Portevin D;Gagneux S;Comas I;Young D
本研究的目的是确定人类结核分枝杆菌复合体（MTBC）代表全球多样性的一组临床分离株之间的系统发育关系和炎症反应之间是否存在相关性。从受感染的人外周血单核细胞衍生的巨噬细胞的细胞因子的测量揭示了对不同菌株的反应的广泛变化。对于不同的促炎细胞因子和趋化因子，观察到对单个菌株的高或低应答的相同模式，并且在多个人类供体中是保守的。虽然MTBC的每个主要系统发生谱系包括诱导一系列细胞因子应答的菌株，但我们发现总体炎症表型在谱系之间显著不同。特别是，进化上的现代谱系的比较表明，一个显着的倾向于较低的早期炎症反应。在自体单核细胞来源的树突状细胞和小鼠骨髓来源的巨噬细胞中也观察到使用GM-CSF来源的巨噬细胞观察到的对古代和现代谱系的差异反应，但在人未分级外周血单核细胞中未观察到。我们假设，对现代谱系的免疫反应降低有助于更快的疾病进展和传播，这可能是人口扩大背景下的选择性优势。除了谱系效应之外，在结核病疫苗开发中还需要考虑MTBC引起的先天免疫应答中的大菌株间差异。 结核分枝杆菌是一种长期存在的人类病原体，通过气溶胶传播在密切的社会群体中相互作用的个体之间传播。可以预见，M.结核病将与人类社会的进化平行，并且通过临床分离株的全基因组测序确定的遗传学确实与病原体在非洲与现代人类的出现及其随后沿人类迁移和贸易沿着传播一致。本研究旨在验证M.结核病分离株将反映在其生物学特性的相应多样性中。特别是，我们探讨了不同的分离株与先天免疫系统的相互作用，这在初始抵抗感染和疾病传播中起着重要的对比作用。我们观察到先天免疫反应的差异，当我们比较分离属于“现代”血统，在最近大规模人口扩张的地区的高密度人群中进化，与分离属于“古老”血统，在较老的低密度人群中选择。我们的研究结果提供了深入了解宿主-病原体的共同进化和根本机制的发病机制的M。结核
The aim of the present study was to determine whether there is a correlation between phylogenetic relationship and inflammatory response amongst a panel of clinical isolates representative of the global diversity of the human Mycobacterium tuberculosis Complex (MTBC). Measurement of cytokines from infected human peripheral blood monocyte-derived macrophages revealed a wide variation in the response to different strains. The same pattern of high or low response to individual strains was observed for different pro-inflammatory cytokines and chemokines, and was conserved across multiple human donors. Although each major phylogenetic lineage of MTBC included strains inducing a range of cytokine responses, we found that overall inflammatory phenotypes differed significantly across lineages. In particular, comparison of evolutionarily modern lineages demonstrated a significant skewing towards lower early inflammatory response. The differential response to ancient and modern lineages observed using GM-CSF derived macrophages was also observed in autologous monocyte-derived dendritic cells and murine bone marrow-derived macrophages, but not in human unfractionated peripheral blood mononuclear cells. We hypothesize that the reduced immune responses to modern lineages contribute to more rapid disease progression and transmission, which might be a selective advantage in the context of expanding human populations. In addition to the lineage effects, the large strain-to-strain variation in innate immune responses elicited by MTBC will need to be considered in tuberculosis vaccine development. Mycobacterium tuberculosis is a long-standing human pathogen spread by aerosol transmission between individuals interacting in close social groups. It can be anticipated that the evolution of M. tuberculosis will parallel the evolution of human societies, and the phylogeny as determined by whole genome sequencing of clinical isolates is indeed consistent with emergence of the pathogen with modern humans in Africa and its subsequent dissemination along routes of human migration and trade. The present study was designed to test the hypothesis that the genetic diversity of M. tuberculosis isolates would be reflected in a corresponding diversity in their biological properties. In particular, we explored the interaction of different isolates with the innate immune system, which plays important contrasting roles in initial resistance to infection and in disease transmission. We observed a difference in the innate immune response when we compared isolates belonging to “modern” lineages that have evolved amongst high-density populations in regions of recent massive demographic expansion, with isolates belonging to “ancient” lineages selected in older low-density human populations. Our results provide insights into host-pathogen co-evolution and into fundamental mechanisms underlying the pathogenesis of M. tuberculosis.
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DOI：
10.1073/pnas.0604283103
发表时间：
2006-10-17
影响因子：
11.1
作者：
Newton, Sandra M.;Smith, Rebecca J.;Wilkinson, Robert J.
通讯作者：
Wilkinson, Robert J.
影响因子：
9.4
作者：
Kong, Y.;Cave, M. D.;Yang, Z. H.
通讯作者：
Yang, Z. H.
DOI：
10.1016/j.ddmec.2010.09.004
发表时间：
2010
期刊：
Drug discovery today. Disease mechanisms
影响因子：
--
作者：
Coscolla, Mireilla;Gagneux, Sebastien
通讯作者：
Gagneux, Sebastien
C 型凝集素 Mincle 直接识别分枝杆菌糖脂、海藻糖二霉菌酸酯。
影响因子：
15.3
作者：
Ishikawa, Eri;Ishikawa, Tetsuaki;Morita, Yasu S.;Toyonaga, Kenji;Yamada, Hisakata;Takeuchi, Osamu;Kinoshita, Taroh;Akira, Shizuo;Yoshikai, Yasunobu;Yamasaki, Sho
通讯作者：
Yamasaki, Sho
影响因子：
6.7
作者：
Caws M;Thwaites G;Dunstan S;Hawn TR;Lan NT;Thuong NT;Stepniewska K;Huyen MN;Bang ND;Loc TH;Gagneux S;van Soolingen D;Kremer K;van der Sande M;Small P;Anh PT;Chinh NT;Quy HT;Duyen NT;Tho DQ;Hieu NT;Torok E;Hien TT;Dung NH;Nhu NT;Duy PM;van Vinh Chau N;Farrar J
通讯作者：
Farrar J