Tuberculosis最新文献

英文中文

Dysregulated IFN-γ, IL-6 and TNF-α after COVID-19 is suggestive of lowered innate immune responses to SARS-CoV-2 and MTB COVID-19后IFN-γ、IL-6和TNF-α的失调提示对SARS-CoV-2和MTB的先天免疫应答降低

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2026-01-01 Epub Date: 2025-12-02 DOI: 10.1016/j.tube.2025.102718

Uzair Abbas , Kiran Iqbal Masood , Tulaib Iqbal , Shama Qaiser , Martin Rottenberg , Bushra Jamil , Rabia Hussain , Zahra Hasan

SARS-CoV-2 infection modulates innate and adaptive immunity and likely impacts outcomes of infections such as Mycobacterium tuberculosis (MTB). We investigated the association between COVID-19 and latent tuberculosis infection (LTBi), studying viral and mycobacterial antigen-stimulated responses in those with and without a history of COVID-19.

We studied healthy Controls and COVID-19 convalescent subjects. Participants were screened for LTBi using an interferon-gamma release assay (IGRA). SARS-CoV-2 Spike- and MTB H37Rv-sonicate -stimulated cytokines from peripheral blood mononuclear cells (PBMCs) were measured.

Spike-induced IFN-γ (p = 0.03), IL-6 (p = 0.018) and IL-2 (p = 0.04) levels were reduced in COVID-19 as compared with Controls. Within Controls, Spike induced higher cytokine levels in IGRA positive participants (p < 0.05). MTB-induced IFN-γ (0.003), IL-2 (p = 0.0021), IL-6 (p = 0.002), TNF-α (p = 0.02), and IL-10 (p = 0.04) levels were lowered in COVID-19. MTB- stimulated higher levels of proinflammatory cytokines were found in IGRA-positive Controls. Between IGRA positive participants, the COVID-19 group displayed lower Spike and MTB induced IFN-γ (0.003), IL-6 (0.0037), IL-2 (0.001), and TNF-α (0.005) levels. Further, MTB-induced IL-6/IL-10 and TNF-α/IL-10 ratios were higher in COVID-IGRA positive participants.

Reduced SARS-CoV-2 and MTB activation of inflammatory cytokines reflects downregulated immunity after COVID-19. Further studies are required to assess whether LTBi and COVID-19 increase the risk of progression to tuberculosis.

SARS-CoV-2感染可调节先天免疫和适应性免疫，并可能影响结核分枝杆菌（MTB）等感染的结果。我们研究了COVID-19与潜伏结核感染（LTBi）之间的关系，研究了有和没有COVID-19病史的人的病毒和分枝杆菌抗原刺激反应。我们研究了健康对照和COVID-19恢复期受试者。参与者使用干扰素- γ释放试验（IGRA）筛选LTBi。检测外周血单个核细胞（PBMCs）受SARS-CoV-2 Spike和MTB h37rv声波刺激的细胞因子。与对照组相比，COVID-19患者的峰值诱导的IFN-γ (p = 0.03)、IL-6 （p = 0.018）和IL-2 （p = 0.04）水平降低。在对照组中，Spike诱导IGRA阳性参与者的细胞因子水平升高（p < 0.05）。MTB-induced干扰素-γ(0.003),2 (p = 0.0021), il - 6 (p = 0.002),肿瘤坏死因子-α(p = 0.02)和il - 10 (p = 0.04)水平在COVID-19降低。在igra阳性对照中发现MTB刺激的促炎细胞因子水平较高。在IGRA阳性的参与者中，COVID-19组表现出较低的Spike和MTB诱导的IFN-γ(0.003)、IL-6（0.0037）、IL-2（0.001）和TNF-α(0.005)水平。此外，mtb诱导的IL-6/IL-10和TNF-α/IL-10比值在COVID-IGRA阳性参与者中较高。SARS-CoV-2和MTB炎症细胞因子激活降低反映了COVID-19后免疫下调。需要进一步的研究来评估LTBi和COVID-19是否会增加进展为结核病的风险。

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引用次数: 0

Response to “Constructive appraisal of Zhong et al.’s study on Mycobacterium tuberculosis dormant antigens and PB2-DIMQ vaccine: Opportunities for translational strengthening” 对Zhong等人关于结核分枝杆菌休眠抗原和PB2-DIMQ疫苗研究的建设性评价：加强翻译的机会的回应。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2026-01-01 Epub Date: 2025-12-18 DOI: 10.1016/j.tube.2025.102723

Qiangsen Zhong , Xiaochun Wang , Yun Xu , Runlin Wang , Mingming Zhou , Xinkuang Liu

引用次数: 0

Responses to comments on “A comparative study between milk- and serum-based antibody detection assays for Johne's disease in New Zealand dairy cattle” 对“新西兰奶牛约翰氏病乳基抗体检测与血清抗体检测的比较研究”评论的答复

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2026-01-01 Epub Date: 2025-12-11 DOI: 10.1016/j.tube.2025.102721

K.M. Venkatesh , Nicolas Lopez-Villalobos , Sandeep K. Gupta , Garry B. Udy , Richard Laven , Shih-Jiuan Chiu , Piyush Bugde , Yoichi Furuya , Venkata Sayoji Rao Dukkipati

引用次数: 0

Comments on “A comparative study between milk- and serum-based antibody detection assays for Johne's disease in New Zealand dairy cattle” 对“新西兰奶牛约翰氏病乳抗体和血清抗体检测方法的比较研究”的评论。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2026-01-01 Epub Date: 2025-12-09 DOI: 10.1016/j.tube.2025.102719

Arun Kumar, Ankur Sharma, Saumya Das, Preeti Dnyandeo Sonje, Dhanya Dedeepya

引用次数: 0

Diagnostic value of five Mycobacterium tuberculosis dormant highly expressed antigens in latent infections and immunogenicity assessment of a novel subunit vaccine PB2-DIMQ 5种结核分枝杆菌高表达抗原在潜伏感染中的诊断价值及新型亚单位疫苗PB2-DIMQ的免疫原性评价

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-12-01 Epub Date: 2025-10-14 DOI: 10.1016/j.tube.2025.102698

Qiangsen Zhong , Xiaochun Wang , Yun Xu , Runlin Wang , Mingming Zhou , Xinkuang Liu

Tuberculosis (TB) is the leading cause of death in global infectious diseases, and precise diagnosis and preventive intervention of latent tuberculosis infection (LTBI) are important to end the TB epidemic. In this study, we explored the diagnostic value of five Mycobacterium tuberculosis (MTB) dormant highly expressed antigens (Rv0470c, Rv2026c, Rv2466c, Rv3334, and Rv3406) in LTBI and evaluated the immunologic efficacy of a novel subunit vaccine, PB2-DIMQ (antigen PB2:Rv0470c-Rv1846c; adjuvant DIMQ: liposome dimethyl dioctadecylammonium bromide [DDA] + imiquimod [IMQ]). It was found that all five antigens were generally capable of eliciting immune responses among patients with LTBI and those with active tuberculosis (ATB). Although differences in the intensity of responses were present for some antigens between the two groups, their discriminatory power in differentiating LTBI from ATB was limited (AUC = 0.6622–0.7473). Nevertheless, these antigens still hold promising potential for application in the diagnosis of MTB infection (AUC = 0.7415–0.9556). On the other hand, under the prime-boost strategy, the PB2-DIMQ vaccine induced a significantly stronger Th1-type immune response than BCG in a mouse model, promoting the expansion of multifunctional T cells (CD4⁺/CD8⁺ IFN-γ⁺ IL-2⁺), and enhanced in vitro bacterial inhibition. This study provides new targets and strategies (fusion antigen PB2 + adjuvant DIMQ) for the development of novel TB diagnostic tools and next-generation TB vaccines with important clinical translational prospects.

结核病（TB）是全球传染病中导致死亡的主要原因，对潜伏性结核感染（LTBI）的准确诊断和预防干预对终结结核病流行具有重要意义。本研究探讨了5种结核分枝杆菌（MTB）休眠高表达抗原（Rv0470c、Rv2026c、Rv2466c、Rv3334和Rv3406）在LTBI中的诊断价值，并评价了一种新型亚单位疫苗PB2-DIMQ（抗原PB2:Rv0470c- rv1846c；佐剂DIMQ：脂质体二甲基二十八烷基溴化铵[DDA] +咪喹莫特[IMQ]）的免疫效果。结果发现，这五种抗原在LTBI和活动性肺结核（ATB）患者中普遍能引起免疫应答。尽管两组之间对某些抗原的反应强度存在差异，但它们区分LTBI和ATB的能力有限（AUC = 0.6622-0.7473）。尽管如此，这些抗原在MTB感染的诊断中仍有很大的应用潜力（AUC = 0.7415-0.9556）。另一方面，在启动-增强策略下，PB2-DIMQ疫苗在小鼠模型中诱导的th1型免疫应答明显强于BCG，促进了多功能T细胞（CD4+/CD8+ IFN-γ+ IL-2+）的扩增，并增强了体外细菌抑制作用。该研究为开发新型结核病诊断工具和下一代结核病疫苗提供了新的靶点和策略（融合抗原PB2 +佐剂DIMQ），具有重要的临床转化前景。

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引用次数: 0

Diagnosing tuberculous meningitis from cell-free DNA by multi-targeted real-time PCR: An experience from 170 cases 多靶点实时PCR检测游离DNA诊断结核性脑膜炎170例的经验。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-12-01 Epub Date: 2025-10-29 DOI: 10.1016/j.tube.2025.102705

Kusum Sharma , Megha Sharma , Ritu Shree , Neeraj Singla , Himanshu Joshi , Ashish Kumar Kakkar , Apinderpreet Singh , Aman Sharma , Navneet Sharma , Manish Modi

Setting

and objective: To evaluate the diagnostic utility of Cell-free DNA (Cf-DNA)-based multi-targeted real-time PCR (Mrt-PCR) for diagnosing tuberculous meningitis, the most severe form of extrapulmonary tuberculosis.

Design

A total of 170 cerebrospinal fluid samples (CSF) of tuberculous meningitis [Definite TBM (n = 146), Probable TBM (n = 24)] and 100 non-TB controls were subjected to Cf-DNA Mrt-PCR test using IS6110, IS1081, and nrdZ gene targets. The performance was also evaluated against Truenat MTB Plus assay and GeneXpert MTB/RIF Ultra.

Results

The sensitivity, specificity, positive predictive value and negative predictive value of Cf-DNA M-rtPCR was 78.24 %, 100 %, 100 % and 72.99 %, respectively in overall diagnosis of TBM and 82.88 %, 100 %, 100 % and 80 %, respectively in diagnosing ‘definite’ TBM. Cf-DNA M-rtPCR detected 14 additional cases that were missed by Truenat MTB Plus assay and GeneXpert MTB/RIF Ultra. Among the different gene targets used, eight cases were detected only by IS1081, three only by IS6110 and one only by nrdZ gene. Six cases were reported rifampicin-resistant by both Truenat MTB Plus assay and GeneXpert MTB/RIF Ultra and were also confirmed by rpoB sequencing.

Conclusion

The detection of cell-free DNA, along with M-rtPCR could serve as a reliable tool for diagnosing tuberculous meningitis directly from CSF samples.

背景和目的：评估基于无细胞DNA （Cf-DNA）的多目标实时PCR （Mrt-PCR）诊断结核性脑膜炎（最严重的肺外结核形式）的诊断效用。设计：采用IS6110、IS1081和nrdZ基因靶点，对170例结核性脑膜炎（确诊结核性脑膜炎（n = 146）、疑似结核性脑膜炎（n = 24））患者脑脊液样本（CSF）和100例非结核性脑膜炎对照进行Cf-DNA rt- pcr检测。还对Truenat MTB Plus试验和GeneXpert MTB/RIF Ultra进行了性能评估。结果：Cf-DNA M-rtPCR对TBM的总体诊断敏感性为78.24%，特异性为100%，阳性预测值为100%，阴性预测值为72.99%；对TBM的“明确”诊断敏感性为82.88%，特异性为100%，阳性预测值为100%，阴性预测值为80%。Cf-DNA M-rtPCR检测到Truenat MTB Plus试验和GeneXpert MTB/RIF Ultra未检测到的另外14例病例。在所使用的不同基因靶点中，仅IS1081检测到8例，仅IS6110检测到3例，仅nrdZ检测到1例。Truenat MTB Plus试验和GeneXpert MTB/RIF Ultra均报告6例对利福平耐药，并通过rpoB测序证实。结论：游离DNA检测结合m -rt - pcr可作为直接从脑脊液中诊断结核性脑膜炎的可靠工具。

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引用次数: 0

Epigenetic regulation of the immune response to Mycobacterium bovis infection in cattle: potential implications for diagnostic test sensitivity 牛对牛分枝杆菌感染免疫反应的表观遗传调控：对诊断试验敏感性的潜在影响。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-12-01 Epub Date: 2025-10-10 DOI: 10.1016/j.tube.2025.102697

Eamonn Gormley , David E. MacHugh , Kieran G. Meade

As a zoonotic disease, with a global impact on animal health, welfare and trade, bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, has been subject to strict control measures in many countries to reduce the impact of the disease on cattle and their handlers. However, eradication efforts have been constrained in some countries for several reasons, including limitations in diagnostic test sensitivity. As a result, a proportion of M. bovis-infected cattle are being misdiagnosed, which then become reservoirs of infection contributing to further spread of disease. A significant amount of research effort has focused on understanding the immune responses to M. bovis infection in cattle and on investigating how these can be leveraged to improve diagnostic performance. More recently, and predominantly in human and murine models of Mycobacterium tuberculosis infection, there has been a growing recognition that chemical modifications to DNA and proteins (referred collectively to as epigenetic mechanisms), which spatially govern gene activity across host chromosomes, can directly regulate the immune responses. However, knowledge of epigenetic changes in response to M. bovis infection in cattle is still in its infancy. Epigenetic “marks” (e.g., DNA methylation and histone modifications) are dynamic, and alterations induced by the infecting pathogen lead to a complex biochemical interplay that can ultimately determine the infection outcome. Drawing on the extensive wealth of epigenetic findings from studies on M. tuberculosis infection, this review explores the evidence for epigenetic control of the immune response to M. bovis and bTB disease by methylation and acetylation of host chromosomes. Understanding the extent and nature of epigenetic control may reveal how M. bovis coevolution with the bovine host shapes both immune outcomes and diagnostic test sensitivity.

作为一种对动物健康、福利和贸易产生全球性影响的人畜共患疾病，牛结核（bTB）是由牛分枝杆菌感染引起的，在许多国家受到严格的控制措施，以减少该疾病对牛及其处理者的影响。然而，由于几种原因，包括诊断测试敏感性的限制，根除工作在一些国家受到限制。结果，一部分感染牛分枝杆菌的牛被误诊，然后成为感染的宿主，导致疾病进一步传播。大量的研究工作集中在了解牛对牛分枝杆菌感染的免疫反应，并研究如何利用这些反应来提高诊断性能。最近，主要是在人类和小鼠结核分枝杆菌感染模型中，人们越来越认识到DNA和蛋白质的化学修饰（统称为表观遗传机制）可以直接调节宿主染色体上的基因活性，从而在空间上控制宿主染色体上的基因活性。然而，对牛对牛分枝杆菌感染反应的表观遗传变化的了解仍处于起步阶段。表观遗传“标记”（例如，DNA甲基化和组蛋白修饰）是动态的，由感染病原体诱导的改变导致复杂的生化相互作用，最终决定感染结果。根据对结核分枝杆菌感染研究的大量表观遗传学发现，本综述探讨了宿主染色体甲基化和乙酰化对牛分枝杆菌和bTB疾病免疫反应的表观遗传学控制的证据。了解表观遗传控制的程度和性质可能揭示牛分枝杆菌与牛宿主的共同进化如何影响免疫结果和诊断测试敏感性。

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引用次数: 0

Restriction of the main lineages of Mycobacterium africanum to West Africa: Insights from host-pathogen interaction studies 非洲分枝杆菌主要谱系在西非的限制：来自宿主-病原体相互作用研究的见解。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-12-01 Epub Date: 2025-10-24 DOI: 10.1016/j.tube.2025.102701

Theophilus Afum, Prince Asare, Stephen Osei-Wusu, Dorothy Yeboah-Manu

Tuberculosis (TB), a disease of old, continues to plague humans after its declaration as a global health emergency in 1993. Over the years, studies have focused on understanding the causative pathogen, Mycobacterium tuberculosis complex (MTBC), and its interaction with humans from TB infection to progression to active disease. It is now known that MTBC lineage diversity impacts several disease presentations and outcomes, including disease progression and severity, virulence and antimicrobial resistance, transmissibility, and host response. Some of these lineages are highly geographically restricted, and prominent amongst them are lineages 5 and 6 of Mycobacterium africanum (Maf), mainly found in West Africa, with cases outside of this region usually prevalent in individuals of West African descent. Several hypotheses have been propounded to investigate these restrictions, ranging from the locality of an animal reservoir in certain areas to the emigration of Maf into West Africa but not spreading globally because Mycobacterium tuberculosis sensu stricto (Mtbss) outcompeted it. Another hypothesis, which states that host genetic factors can influence host susceptibility to some MTBC lineages, as well as TB progression to the severe disease state, appears more widely accepted. However, the exact mechanisms mediating this susceptibility have not been fully explored. This review seeks to highlight the advances made towards understanding the geographical restrictions of Maf and the host-pathogen interactions leading to the coevolution of Maf and humans in West Africa.

结核病是一种古老的疾病，在1993年被宣布为全球卫生紧急情况后，它继续困扰着人类。多年来，研究的重点是了解致病病原体结核分枝杆菌复合体（MTBC）及其与人类从结核感染到进展为活动性疾病的相互作用。现在已知MTBC谱系多样性影响几种疾病的表现和结果，包括疾病进展和严重程度、毒力和抗微生物药物耐药性、传播性和宿主反应。其中一些谱系在地理上受到高度限制，其中突出的是非洲分枝杆菌（Maf）的谱系5和6，主要在西非发现，该地区以外的病例通常在西非后裔中流行。已经提出了几种假设来调查这些限制，从某些地区的动物宿主到Maf移民到西非，但由于严格意义结核分枝杆菌（Mtbss）的竞争而没有在全球传播。另一种假说，即宿主遗传因素可以影响宿主对某些MTBC谱系的易感性，以及结核病向严重疾病状态的进展，似乎得到了更广泛的接受。然而，介导这种易感性的确切机制尚未得到充分探索。这篇综述旨在强调在了解Maf的地理限制和导致Maf与西非人类共同进化的宿主-病原体相互作用方面取得的进展。

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引用次数: 0

Response to “Correspondence on ‘Utility of pleural fluid-derived extracellular vesicles as a source of Mycobacterium tuberculosis antigens MPT51 and MPT64 for pleural TB diagnosis: a proof-of-concept study” 对“胸膜液来源的细胞外囊泡作为结核分枝杆菌抗原MPT51和MPT64在胸膜结核诊断中的应用：一项概念验证研究”的回应。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-12-01 Epub Date: 2025-10-25 DOI: 10.1016/j.tube.2025.102699

Neha Jindal, Manisha Dass, Pratibha Sharma, Sagarika Haldar

引用次数: 0

Knockdown of argininosuccinate lyase influences the growth of Mycolicibacterium smegmatis in vitro and in vivo 精氨酸琥珀酸裂解酶的敲低对耻垢分枝杆菌体外和体内生长的影响

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-12-01 Epub Date: 2025-09-19 DOI: 10.1016/j.tube.2025.102693

Yufan Xu , Longlong Wang , Jijie Jiang , Guocheng Zhao , Zhe Wang

The rising prevalence of drug-resistant tuberculosis (DR-TB), coupled with stagnation in the development of novel therapeutics, underscores the urgent need for new drug targets and innovative anti-tuberculosis agents. In this study, we demonstrate that CRISPR interference-mediated knockdown of argH, a nitrogen metabolism-associated gene encoding argininosuccinate lyase, significantly impairs the growth of Mycolicibacterium smegmatis (formerly Mycobacterium smegmatis). This growth defect was alleviated in a concentration-dependent manner by arginine supplementation. In a goldfish infection model, argH knockdown led to a marked reduction in bacterial burden within both liver and kidney tissues. Notably, bacitracin and 5-fluorouracil exhibited synergistic effects when combined with argH knockdown. Metabolomic profiling revealed significant perturbations in multiple amino acids, as well as in succinyl-CoA and lactate levels, suggesting that suppression of argH impairs M. smegmatis proliferation by disrupting amino acid homeostasis and interfering with aerobic respiration.

耐药结核病（DR-TB）的流行率不断上升，加上新疗法的开发停滞不前，突显出迫切需要新的药物靶点和创新的抗结核药物。在这项研究中，我们证明了CRISPR干扰介导的argH（一种编码精氨酸琥珀酸裂解酶的氮代谢相关基因）的敲低会显著损害耻垢分枝杆菌（原耻垢分枝杆菌）的生长。通过补充精氨酸，这种生长缺陷以浓度依赖性的方式得到缓解。在金鱼感染模型中，敲低argH导致肝脏和肾脏组织内细菌负担显著减少。值得注意的是，杆菌肽和5-氟尿嘧啶在与argH下调联合使用时表现出协同效应。代谢组学分析显示，多种氨基酸以及琥珀酰辅酶a和乳酸水平受到显著干扰，表明抑制argH通过破坏氨基酸稳态和干扰有氧呼吸来损害耻毛分枝杆菌的增殖。

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