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 : 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 “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 DOI: 10.1016/j.tube.2025.102699

Neha Jindal, Manisha Dass, Pratibha Sharma, Sagarika Haldar

引用次数: 0

Inhibition of mycobacteria proliferation in macrophages by diaryl ether derivatives of Dehydrozingerone compound and repurposed drugs (Rebamipide, Sofalcone) via NF-κB pathway inhibition Dehydrozingerone化合物二芳基醚衍生物和Rebamipide、Sofalcone通过抑制NF-κB通路抑制巨噬细胞分枝杆菌增殖

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-12-01 DOI: 10.1016/j.tube.2025.102706

Safiya Mehraj , Shazia Ali , Chetan Kumar , Asif Ali , Zahoor Ahmad

Background

Chronic inflammation fuels tissue damage and morbidity in numerous diseases, including Tuberculosis, underscoring the vital need for Host-Directed Therapies to safely modulate the exaggerated host response. We investigated the immunomodulatory potential of Sofalcone and Rebamipide alongside a novel Diaryl Ether derivative of Dehydrozingerone DHZ (6), hypothesizing that they exert therapeutic effects by targeting the central inflammatory driver, the NF-κB pathway.

Methods

We evaluated the safety and efficacy of the compounds in THP-1 macrophages infected with M. smegmatis. Mechanistic studies utilized Western blotting, immunofluorescence, and ELISA to track NF-κB activation. MMP activity was assessed by gelatin zymography, and ROS production was quantified using the DCFH-DA assay.

Results

All compounds exhibited low cytotoxicity and significantly reduced intracellular bacterial survival. Agents potently and consistently inhibited the NF-κB cascade, evidenced by ≈ 83 % suppression of upstream P-IKKα/IKKβ and up to ≈89 % reduction in p65 phosphorylation. This molecular blockade prevented p65 nuclear translocation and resulted in a downstream functional benefit: near total abolition of MMP-2/9 activity and ≈71 % mitigation of ROS production.

Conclusion

Our results unequivocally validate NF-κB inhibition by DHZ (6), Sofalcone, and Rebamipide as a powerful strategy for HDT. These compounds are promising adjunct therapies to suppress host inflammation and limit tissue damage.

慢性炎症会导致包括结核病在内的许多疾病的组织损伤和发病率，这强调了对宿主导向疗法的迫切需要，以安全地调节过度的宿主反应。我们研究了Sofalcone和Rebamipide以及Dehydrozingerone DHZ的新型二芳基醚衍生物的免疫调节潜力(6)，假设它们通过靶向中枢炎症驱动因子NF-κB途径发挥治疗作用。方法评价化合物对耻垢分枝杆菌感染的THP-1巨噬细胞的安全性和有效性。机制研究采用Western blotting、免疫荧光和ELISA追踪NF-κB活化。明胶酶谱法测定MMP活性，DCFH-DA法测定ROS产量。结果所有化合物均表现出较低的细胞毒性，并显著降低细胞内细菌存活率。药物有效且持续地抑制NF-κB级联，上游P-IKKα/IKKβ抑制约83%，p65磷酸化降低约89%。这种分子阻断阻止了p65核易位，并导致下游功能获益：MMP-2/9活性几乎完全消除，ROS产生减少约71%。结论：我们的研究结果明确证实了DHZ(6)、Sofalcone和Rebamipide对NF-κB的抑制是治疗HDT的有效策略。这些化合物是抑制宿主炎症和限制组织损伤的有希望的辅助疗法。

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引用次数: 0

Letter to Editor: manuscript entitled “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” by Jindal et al. published in Tuberculosis150 (2025) 102578 致编辑的信：由Jindal等人撰写的题为“胸膜液来源的细胞外囊泡作为结核分枝杆菌抗原MPT51和MPT64用于胸膜结核诊断的效用：一项概念验证研究”的手稿，发表在结核菌150(2025)102578上。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-12-01 DOI: 10.1016/j.tube.2025.102695

Promod K. Mehta

引用次数: 0

A comparative study between milk- and serum-based antibody detection assays for Johne's disease in New Zealand dairy cattle 新西兰奶牛约翰氏病乳基抗体检测与血清基抗体检测的比较研究。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-12-01 DOI: 10.1016/j.tube.2025.102679

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

Dairy cattle are affected by Johne's disease. It is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Suboptimal diagnostic tests add more to the productivity loss resulting from this disease. Agreement between and within different commercial kits is crucial in the decision-making process of disease surveillance programmes. This study compared two ELISAs, that is, Johne's disease commercial antibody detection kits (A and B), using milk and serum samples from New Zealand dairy cattle. These results were also compared with a subset of faecal PCR results. Five scenarios were considered for the comparison of ELISA tests. The point estimates of kappa coefficients (k) between the serum (0.84–0.94) assays were higher than the milk assays (0.59–0.82). The point estimates of kappa coefficients between serum and milk ELISA outcomes were higher for kit B (k = 0.79–0.86) than for kit A (k = 0.55–0.79). The point estimates of kappa coefficients between the ELISA and faecal PCR outcomes varied between 0.43 and 0.74. ELISA tests had point estimates of sensitivity ranging from 0.67 to 0.88 and specificity from 0.62 to 0.93, relative to the faecal PCR test. Results suggest that serum provides a better choice of sample type when both commercial kits A and B are used for Johne's disease surveillance of dairy cattle in New Zealand. Milk assays can be cost-effective to diagnose MAP-positive animals; kit B can be best suited for New Zealand conditions, provided the repeatability of the results is validated.

奶牛受到约翰氏病的影响。它是由鸟分枝杆菌亚种副结核（MAP）引起的。不理想的诊断测试增加了该疾病造成的生产力损失。在疾病监测规划的决策过程中，不同商业试剂盒之间和内部的协议至关重要。本研究比较了两种elisa，即约翰氏病商业抗体检测试剂盒（A和B），使用的是新西兰奶牛的牛奶和血清样本。这些结果还与粪便PCR结果的一个子集进行了比较。我们考虑了五种情况对ELISA检测结果进行比较。血清测定法的kappa系数(k)点估计值（0.84-0.94）高于乳汁测定法（0.59-0.82）。试剂盒B （k = 0.79-0.86）比试剂盒A （k = 0.55-0.79）血清和牛奶ELISA结果之间kappa系数的点估计值更高。ELISA和粪便PCR结果之间的kappa系数点估计值在0.43和0.74之间变化。相对于粪便PCR检测，ELISA检测的点估计灵敏度为0.67 ~ 0.88，特异性为0.62 ~ 0.93。结果表明，在对新西兰奶牛进行约翰氏病监测时，血清是一种更好的样品类型选择。乳汁分析对于诊断map阳性动物具有成本效益；试剂盒B最适合新西兰的条件，前提是结果的可重复性得到验证。

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引用次数: 0

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。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-11-19 DOI: 10.1016/j.tube.2025.102708

Parth Aphale , Shashank Dokania , Himanshu Shekhar

引用次数: 0

CountFU: Ditching CFUs for qPCR enumeration of Mycobacterium tuberculosis and a call to join the revolution CountFU：放弃cfu，采用qPCR枚举结核分枝杆菌，并呼吁加入革命

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-11-19 DOI: 10.1016/j.tube.2025.102709

Jason D. Limberis , Alina Nalyvayko , Alexander Mohapatra , Rania Bouzeyen , Zach Howard , Weihao Zheng , John Z. Metcalfe

引用次数: 0

Minimal immune cell subset differences in a cohort of close contacts of tuberculosis index cases 结核病指数病例密切接触者队列中最小免疫细胞亚群差异

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-11-15 DOI: 10.1016/j.tube.2025.102707

Sudhasini Panda , Catherine Cheng , Naomi Hillery , Donald G. Catanzaro , Nelly Ciobanu , Valeriu Crudu , Timothy Rodwell , Antonino Catanzaro , Julie G. Burel , Bjoern Peters , Cecilia S. Lindestam Arlehamn

Understanding the perturbations in immune response across the spectrum of TB infection is still unclear. Here, we followed close contacts of pulmonary TB patients with serial QFT testing at 0, 3, 6, and 12 months, and stratified them into six subgroups: QFT-increasing (low/high), QFT-converters (QFT-to QFT+), QFT + stable, and QFT-individuals. Despite these distinct QFT trajectories, we observed minimal differences in immune cell frequencies, activation profiles, and T-helper subset distributions among QFT subgroups, suggesting limited immunological stratification based on QFT dynamics. Ex vivo immune phenotyping, including CD4, CD8, NKT cell frequencies, memory T-cell subsets, and activated T-cells (HLA-DR⁺CD38⁺), failed to distinguish between QFT subgroups, suggesting blood-based immune profiling may not capture subtle immunological transitions among different QFT subgroups. Active TB (ATB) patients showed marked immune alterations, with elevated antigen-specific CD4 T-cells, activated T cells, intermediate monocytes, NK cells at-diagnosis, which declined following treatment, indicating immune recovery. This suggest, while ex vivo immune profiling effectively distinguishes ATB from non-diseased states, it lacks the sensitivity to resolve QFT-based subgroups. Findings suggest either immune similarity among close contacts regardless of QFT status or limits of blood-based profiling in detecting early changes, underscoring the difficulty of distinguishing QFT subgroups with conventional ex vivo approaches.

了解免疫反应的扰动在整个结核病感染谱仍不清楚。在这里，我们对肺结核患者的密切接触者进行了0、3、6和12个月的连续QFT检测，并将他们分为六个亚组：QFT增加（低/高）、QFT转换（从QFT转为QFT+）、QFT稳定和QFT个体。尽管有这些不同的QFT轨迹，我们观察到免疫细胞频率、激活谱和辅助性t细胞亚群分布在QFT亚组之间的差异很小，这表明基于QFT动力学的免疫分层有限。体外免疫表型，包括CD4、CD8、NKT细胞频率、记忆t细胞亚群和活化t细胞（HLA-DR+CD38+），无法区分QFT亚群，这表明基于血液的免疫谱可能无法捕捉不同QFT亚群之间微妙的免疫转变。活动性结核（ATB）患者表现出明显的免疫改变，诊断时抗原特异性CD4 T细胞、活化T细胞、中间单核细胞、NK细胞升高，治疗后下降，表明免疫恢复。这表明，虽然体外免疫谱分析可以有效区分ATB和非病变状态，但它缺乏分辨基于qft的亚群的敏感性。研究结果表明，无论QFT状态如何，密切接触者之间的免疫相似性或基于血液的谱分析在检测早期变化方面的局限性，都强调了用传统的离体方法区分QFT亚群的困难。

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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 : 2025-10-29 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

In vitro and in vivo efficacy of PI3Kγ inhibitor AS605240 in controlling mycobacterial infections PI3Kγ抑制剂AS605240控制分枝杆菌感染的体内外疗效观察

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis

Pub Date : 2025-10-29 DOI: 10.1016/j.tube.2025.102704

Valnês da Silva Rodrigues-Junior , Maria Eugênia.G. de Freitas , Maria Gabriella S. Sidrônio , Daniel.W.A. Magalhães , Gisela C. Paulino , Francisco Jaime B. Mendonça-Junior , Sandra Rodrigues-Mascarenhas , Maria Martha Campos

Inhibition of PI3Kγ is an attractive therapeutic target for the development of novel host-directed modulating strategies for the treatment of infectious diseases. This work investigated the antimicrobial potential of AS605240, a selective inhibitor of PI3Kγ, in pre-clinical models of mycobacterial infections. Of note, we observed that treatment with AS605240 effectively reduced both intracellular M. smegmatis and M. tuberculosis counts in RAW 264.7 cells. Moreover, treatment of M. tuberculosis-infected cells with AS605240 increased TNF-α and decreased IL-1β levels compared to the infected group. Importantly, we found that AS605240 is bacteriostatic in the lungs and bactericidal in spleens from M. tuberculosis-infected mice. Our data provide novel evidence on the relevance of PI3Kγ as a novel molecular target for new anti-tubercular drugs.

抑制PI3Kγ是开发新的宿主定向调节策略治疗传染病的一个有吸引力的治疗靶点。本研究研究了PI3Kγ选择性抑制剂AS605240在分枝杆菌感染临床前模型中的抗菌潜力。值得注意的是，我们观察到用AS605240治疗可以有效降低RAW 264.7细胞内耻垢分枝杆菌和结核分枝杆菌的计数。此外，与感染组相比，用AS605240处理结核分枝杆菌感染细胞增加了TNF-α，降低了IL-1β水平。重要的是，我们发现AS605240在结核分枝杆菌感染小鼠的肺中具有抑菌作用，在脾脏中具有杀菌作用。我们的数据为PI3Kγ作为新型抗结核药物的新分子靶点的相关性提供了新的证据。

引用次数: 0

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