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Host urinary biomarkers in HIV positive and HIV negative patients with tubercular uveitis and other uveitic diseases 患有结核性葡萄膜炎和其他葡萄膜病的 HIV 阳性和 HIV 阴性患者的宿主尿液生物标志物
IF 2.8 3区 医学
Tuberculosis Pub Date : 2024-07-23 DOI: 10.1016/j.tube.2024.102547
Dian P. van der Westhuizen , Candice I. Snyders , Martin Kidd , Gerhard Walzl , Novel N. Chegou , Derrick P. Smit
{"title":"Host urinary biomarkers in HIV positive and HIV negative patients with tubercular uveitis and other uveitic diseases","authors":"Dian P. van der Westhuizen ,&nbsp;Candice I. Snyders ,&nbsp;Martin Kidd ,&nbsp;Gerhard Walzl ,&nbsp;Novel N. Chegou ,&nbsp;Derrick P. Smit","doi":"10.1016/j.tube.2024.102547","DOIUrl":"10.1016/j.tube.2024.102547","url":null,"abstract":"<div><h3>Purpose</h3><p>To determine if host urinary biomarker profiles could distinguish between tubercular uveitis (TBU) and other uveitic diseases (OUD) in patients with and without HIV infection.</p></div><div><h3>Methods</h3><p>Concentrations of 29 different host biomarkers were measured in urine samples using the Luminex platform. Data were analyzed to describe differences between patients diagnosed with and without TBU and with and without HIV co-infection.</p></div><div><h3>Results</h3><p>One-hundred-and-eighteen urine samples were collected and 39% participants were diagnosed as TBU+. Mean age TBU+ was 39.3±13.6 years with 45.7% males. Anterior and panuveitis and unilateral involvement were most common. 32.6% were TBU+HIV+ (median CD4+=215) while 40.2% were OUD+HIV+ (median CD4+=234). Only sVEGF3 was decreased in TBU+ versus OUD+ (p=0.03), regardless of HIV status. Some biomarkers were significantly raised in HIV+ TBU+ compared to HIV- TBU+: sIL-6Rα, CD30, sRAGE , sTNFR I&amp;-II, IP-10, MIP-1β, sEGFR and Ferritin. HIV+ OUD+ had increased sVEGFR3, CD30, sIL-6Rα, IP-10, sTNFR I&amp;-II, Ferritin and Haptoglobin compared to HIV- OUD+. VEGF-A (p = 0.04) was decreased in HIV+ OUD+ versus HIV- OUD+.</p></div><div><h3>Conclusion</h3><p>Decreased urinary concentrations of VEGFR3 were observed in TBU+ compared to TBU-. HIV+ individuals demonstrated increased concentrations of multiple urinary analytes when compared to HIV- patients with uveitis.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102547"},"PeriodicalIF":2.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000738/pdfft?md5=13c131cee83acb721d2afded6319ff35&pid=1-s2.0-S1472979224000738-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Study on the role and molecular mechanism of METTL3-mediated miR-29a-3p in the inflammatory response of spinal tuberculosis METTL3介导的miR-29a-3p在脊柱结核炎症反应中的作用及分子机制研究
IF 2.8 3区 医学
Tuberculosis Pub Date : 2024-07-18 DOI: 10.1016/j.tube.2024.102546
Xiaojun Ma , Yuxin Gao , Zhibo Ren , Hui Dong , Xu Zhang , Ningkui Niu
{"title":"Study on the role and molecular mechanism of METTL3-mediated miR-29a-3p in the inflammatory response of spinal tuberculosis","authors":"Xiaojun Ma ,&nbsp;Yuxin Gao ,&nbsp;Zhibo Ren ,&nbsp;Hui Dong ,&nbsp;Xu Zhang ,&nbsp;Ningkui Niu","doi":"10.1016/j.tube.2024.102546","DOIUrl":"10.1016/j.tube.2024.102546","url":null,"abstract":"<div><h3>Background</h3><p>Spinal Tuberculosis (STB) is a common cause of spinal malformation caused by extrapulmonary tuberculosis in developing countries, which seriously affects the quality of life of patients. It was found that the expression of miRNAs in macrophages was stable, specific and readily available after Mycobacterium tuberculosis (MTB) infection. Our research group determined the differential expression of miR-29a-3p in the vertebra of spinal tuberculosis and intervertebral disc lesions through RNAs chip screening and bioinformatics analysis. However, the specific molecular mechanism of miR-29a-3p in the inflammatory response of spinal tuberculosis remains unclear.</p></div><div><h3>Objective</h3><p>In this study, we mainly discussed the expression of miR-29a-3p in the focal tissue of spinal tuberculosis and the role and molecular mechanism of miR-29a-3p mediated by METTL3 in the inflammatory response of spinal tuberculosis.</p></div><div><h3>Methods</h3><p>The tissues of 15 cases of lumbar degenerative diseases and vertebral lesions of spinal tuberculosis were collected, and the THP-1 macrophage model infected by Mycobacterium tuberculosis was constructed, and verified by qRT-PCR, Western blot, fluorescence in situ hybridization, immunohistochemistry, Cell fluorescence and ELISA.</p></div><div><h3>Results and conclusion</h3><p>We found that the expression of miR-29a-3p was significantly down-regulated in the vertebral body and disc lesion tissues of patients with spinal tuberculosis. Overexpression of miR-29a-3p inhibited the levels of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and inhibition of miR-29a-3p expression promoted the release of the levels of TNF-α, IL-1β and IL-6 inflammatory factors. Our study also shows that knockout of methyltransferase 3 (METTL3) can significantly reduce the expression of miR-29a-3p and promote the release of pro-inflammatory cytokines in macrophages.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102546"},"PeriodicalIF":2.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000726/pdfft?md5=cc5548338614bb1ad9040d2badd745e8&pid=1-s2.0-S1472979224000726-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Preclinical tests for salicylhydrazones derivatives to explore their potential for new antituberculosis agents 对水杨酰肼衍生物进行临床前试验,探索其作为新型抗结核药物的潜力
IF 2.8 3区 医学
Tuberculosis Pub Date : 2024-07-16 DOI: 10.1016/j.tube.2024.102545
Andressa Lorena Ieque , Carolina Trevisolli Palomo , Vitória Gabriela de Freitas Spanhol , Maria Luiza Fróes da Motta Dacome , José Júnior do Carmo Pereira , Francielli Cavalcante Candido , Katiany Rizzieri Caleffi-Ferracioli , Vera Lucia Dias Siqueira , Rosilene Fressatti Cardoso , Fábio Vandresen , Vanessa Guimarães Alves-Olher , Regiane Bertin de Lima Scodro
{"title":"Preclinical tests for salicylhydrazones derivatives to explore their potential for new antituberculosis agents","authors":"Andressa Lorena Ieque ,&nbsp;Carolina Trevisolli Palomo ,&nbsp;Vitória Gabriela de Freitas Spanhol ,&nbsp;Maria Luiza Fróes da Motta Dacome ,&nbsp;José Júnior do Carmo Pereira ,&nbsp;Francielli Cavalcante Candido ,&nbsp;Katiany Rizzieri Caleffi-Ferracioli ,&nbsp;Vera Lucia Dias Siqueira ,&nbsp;Rosilene Fressatti Cardoso ,&nbsp;Fábio Vandresen ,&nbsp;Vanessa Guimarães Alves-Olher ,&nbsp;Regiane Bertin de Lima Scodro","doi":"10.1016/j.tube.2024.102545","DOIUrl":"10.1016/j.tube.2024.102545","url":null,"abstract":"<div><h3>Purpose</h3><p>This study target the synthesis of 22 salicylhydrazones derivatives to apply <em>in vitro</em> screening to explore their potential in the search for new anti-TB prototypes drugs.</p></div><div><h3>Methods</h3><p>The minimum inhibitory concentration (MIC) were evaluated against <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) H<sub>37</sub>Rv and clinical isolates. Drug combination assay, cytotoxicity assay, ethidium bromide accumulation assay (EtBr) and <em>in silico</em> analysis regarding the absorption, distribution, metabolism, excretion and toxicity (ADMET) and pharmacological properties were also performed.</p></div><div><h3>Results</h3><p>Three most promising compounds were selected (10, 11 and 18) to proceed with screening tests. Compound 18 presented the lowest MIC value (0.49 μg/mL) against <em>Mtb</em> H<sub>37</sub>Rv strain, followed by compounds 11 (3.9 μg/mL) and 10 (7.8 μg/mL). All compounds showed activity against drug susceptible and resistant clinical isolates. Cytotoxicity results were promising for all salicylhydrazones, with SI values up to 4,205 for compound 18. The derivative 10 was the only one that demonstrated a non-promising cytotoxicity scenario for a single cell line. All derivatives showed an additive effect (FICI &gt;0.5 to 4.0) in combination with isoniazid, ethambutol and rifampicin.</p></div><div><h3>Conclusion</h3><p>All salicylhydrazones showed potential in the screening tests performed in this study and compound 18 stood out due to its activity against susceptible and resistant bacilli at low concentrations and low cytotoxicity.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102545"},"PeriodicalIF":2.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional analysis of the Mycobacterium bovis AF2122/97 PhoPR system 牛分枝杆菌 AF2122/97 PhoPR 系统的功能分析
IF 2.8 3区 医学
Tuberculosis Pub Date : 2024-07-14 DOI: 10.1016/j.tube.2024.102544
Jose Maria Urtasun-Elizari , Ruoyao Ma , Hayleah Pickford , Damien Farrell , Gabriel Gonzalez , Viktor Perets , Chie Nakajima , Yasuhiko Suzuki , David E. MacHugh , Apoorva Bhatt , Stephen V. Gordon
{"title":"Functional analysis of the Mycobacterium bovis AF2122/97 PhoPR system","authors":"Jose Maria Urtasun-Elizari ,&nbsp;Ruoyao Ma ,&nbsp;Hayleah Pickford ,&nbsp;Damien Farrell ,&nbsp;Gabriel Gonzalez ,&nbsp;Viktor Perets ,&nbsp;Chie Nakajima ,&nbsp;Yasuhiko Suzuki ,&nbsp;David E. MacHugh ,&nbsp;Apoorva Bhatt ,&nbsp;Stephen V. Gordon","doi":"10.1016/j.tube.2024.102544","DOIUrl":"10.1016/j.tube.2024.102544","url":null,"abstract":"<div><p>The PhoPR system is a master regulator in <em>Mycobacterium tuberculosis</em>. A key difference between <em>M</em>. <em>tuberculosis</em> and <em>Mycobacterium bovis</em> is a G71I substitution in the <em>M. bovis</em> PhoR orthologue. Functional studies of the <em>M. bovis</em> PhoPR system have generated conflicting findings, with some research suggesting that the <em>M. bovis</em> PhoPR is defective while others indicate it is functional.</p><p>We sought to revisit the functionality of the <em>M. bovis</em> PhoPR system. To address this, we constructed a <em>phoPR</em> mutant in the reference strain <em>M. bovis</em> AF2122/97. We employed a combination of growth assays and transcriptomics analyses to assess the phenotype of the mutant vs wild type and complemented strains. We found that the <em>M. bovis</em> AF2122/97 Δ<em>phoPR</em> mutant showed a growth defect on solid and liquid media compared to the wild type and complemented strains. The transcriptome of the <em>M. bovis</em> AF2122/97 Δ<em>phoPR</em> mutant was also altered as compared to wild type, including differential expression of genes involved in lipid metabolism and secretion. Our work provides further insight into the activity of PhoPR in <em>M. bovis</em> and underlines the importance of the PhoPR system as a master regulator of gene expression in the <em>Mycobacterium tuberculosis</em> complex.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102544"},"PeriodicalIF":2.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000702/pdfft?md5=02d2a9138ca63808bebfd78f2a56fe26&pid=1-s2.0-S1472979224000702-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141630071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission” [Tuberculosis (2024) 102534] 骨结核基因组调查凸显亚临床肺结核在传播中的作用》[结核病(2024)102534]更正。
IF 2.8 3区 医学
Tuberculosis Pub Date : 2024-07-13 DOI: 10.1016/j.tube.2024.102539
Jinfeng Yin , Guangxuan Yan , Liyi Qin , Chendi Zhu , Jun Fan , Yuwei Li , Junnan Jia , Zhaojun Wu , Hui Jiang , Muhammad Tahir Khan , Jiangdong Wu , Naihui Chu , Howard E. Takiff , Qian Gao , Shibing Qin , Qingyun Liu , Weimin Li
{"title":"Corrigendum to “Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission” [Tuberculosis (2024) 102534]","authors":"Jinfeng Yin ,&nbsp;Guangxuan Yan ,&nbsp;Liyi Qin ,&nbsp;Chendi Zhu ,&nbsp;Jun Fan ,&nbsp;Yuwei Li ,&nbsp;Junnan Jia ,&nbsp;Zhaojun Wu ,&nbsp;Hui Jiang ,&nbsp;Muhammad Tahir Khan ,&nbsp;Jiangdong Wu ,&nbsp;Naihui Chu ,&nbsp;Howard E. Takiff ,&nbsp;Qian Gao ,&nbsp;Shibing Qin ,&nbsp;Qingyun Liu ,&nbsp;Weimin Li","doi":"10.1016/j.tube.2024.102539","DOIUrl":"10.1016/j.tube.2024.102539","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102539"},"PeriodicalIF":2.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000659/pdfft?md5=75905efa7a2e6d8648e3f1438c86f6e9&pid=1-s2.0-S1472979224000659-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Repression of BRD4 mitigates NLRP3 inflammasome-mediated pyroptosis in Mycobacterium-infected macrophages by repressing endoplasmic reticulum stress 通过抑制内质网应激,抑制 BRD4 可减轻分枝杆菌感染的巨噬细胞中 NLRP3 炎症体介导的脓毒症
IF 2.8 3区 医学
Tuberculosis Pub Date : 2024-07-11 DOI: 10.1016/j.tube.2024.102542
Qi-yuan Wang, Xiu-feng Yu, Wen-lan Ji
{"title":"Repression of BRD4 mitigates NLRP3 inflammasome-mediated pyroptosis in Mycobacterium-infected macrophages by repressing endoplasmic reticulum stress","authors":"Qi-yuan Wang,&nbsp;Xiu-feng Yu,&nbsp;Wen-lan Ji","doi":"10.1016/j.tube.2024.102542","DOIUrl":"10.1016/j.tube.2024.102542","url":null,"abstract":"<div><p>Tuberculosis (TB) is the leading cause of human death worldwide due to <em>Mycobacterium tuberculosis</em> (Mtb) infection. Multiple lines of evidences have illuminated the emerging role of NLRP3 inflammasome-mediated pyroptosis in the clearance of pathogenic infection. In the current study, we sought to investigate the functional role and feasible potential mechanism of BRD4 in Mtb-infected macrophages. We observed that BRD4 was distinctly ascended in THP-1 macrophages upon Mtb infection. Functionally, intervention of BRD4 or pretreated with JQ1 obviously restricted Mtb-triggered cell pyroptosis, as evidenced by declination of protein level of the specific pyroptosis markers including Cleaved Caspase 1, gasdermin D (GSDMD-N) and Cleaved-IL-1β. In the meanwhile, disruption of BRD4 or JQ1 application remarkably prohibited excessive inflammatory responses as characterized by reduce the production of the inflammatory factors such as IL-1β and IL-18. Concomitantly, disruption of BRD4 or administrated with JQ1 manifestly repressed Mtb-aroused Nod-like receptor family pyrindomain-containing 3 (NLRP3) inflammasome activation, as witnessed by attenuation of protein levels of NLRP3, Pro-Caspase1 and apoptosis-associated speck-like protein (ASC). The above findings clearly demonstrated that suppression of BRD4 exerted great influence on regulating Mtb-elicited inflammatory response by coordinating NLRP3 inflammasome-mediated pyroptosis. More importantly, perturbation of BRD4 or JQ1 employment notably restrained endoplasmic reticulum (ER) stress triggered by Mtb-infection, as reflected by noticeably lessened the levels of GRP78, CHOP and ATF6. In terms of mechanism, ER stress agonist tunicamycin profoundly abrogated the favorable effects of BRD4 inhibition on Mtb-triggered pyroptosis, inflammation reaction and inflammasome activation. Collectively, these preceding outcomes strongly illuminated that inhibition of BRD4 targeted ER stress to retard NLRP3 inflammasome activation and subsequent cell pyroptosis and prevention of inflammatory response in Mtb-infected macrophages, highlighting that blocking BRD4 might serve as a promising candidate for protection against Mtb-triggered inflammatory injury.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102542"},"PeriodicalIF":2.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optimization of Mycobacterium tuberculosis DNA processing prior to whole genome sequencing 优化全基因组测序前的结核分枝杆菌 DNA 处理。
IF 2.8 3区 医学
Tuberculosis Pub Date : 2024-07-11 DOI: 10.1016/j.tube.2024.102543
Samira Dziri , Julie Marin , Pauline Quagliaro , Charlotte Genestet , Oana Dumitrescu , Etienne Carbonnelle , Typhaine Billard-Pomares
{"title":"Optimization of Mycobacterium tuberculosis DNA processing prior to whole genome sequencing","authors":"Samira Dziri ,&nbsp;Julie Marin ,&nbsp;Pauline Quagliaro ,&nbsp;Charlotte Genestet ,&nbsp;Oana Dumitrescu ,&nbsp;Etienne Carbonnelle ,&nbsp;Typhaine Billard-Pomares","doi":"10.1016/j.tube.2024.102543","DOIUrl":"10.1016/j.tube.2024.102543","url":null,"abstract":"<div><p>The process of whole genome sequencing of the <em>Mycobacterium tuberculosis complex</em> is dependent on complete the inactivation of the strain and subsequent DNA extraction. The objective of this study was to optimise the two steps.</p><p>Firstly, the efficacy of Triton X-100 as a solvent for the inactivation step was evaluated. This solvent has been demonstrated to be effective in killing bacteria and is less toxic than the previously employed chloroform. For the extraction step, two lysis methods were evaluated: enzymatic (B1 protocol) and mechanical (B2 protocol). For whole genome sequencing, the Nextera XT DNA library preparation protocol was performed for both the B1 and B2 protocols. Subsequently, each library was subjected to whole-genome sequencing. The results demonstrated that heat lysis inactivation with Triton was effective, with no bacteria remaining viable following this treatment. The enzymatic and mechanical extraction protocols yielded comparable results in terms of DNA quantity and quality. The sequencing results showed that there was no significant difference in read depths between the two protocols. In conclusion, for MTBC strains, we recommend the use of our Triton inactivation method, which meets biosafety expectations.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102543"},"PeriodicalIF":2.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000696/pdfft?md5=3ca678ea5eb9e059ca535362ab3a5edd&pid=1-s2.0-S1472979224000696-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhanced efficacy of BCG vaccine formulated in adjuvant is dependent on IL-17A expression 用佐剂配制的卡介苗疗效的提高取决于 IL-17A 的表达。
IF 2.8 3区 医学
Tuberculosis Pub Date : 2024-07-06 DOI: 10.1016/j.tube.2024.102540
Steven C. Derrick, Amy Yang, Siobhan Cowley
{"title":"Enhanced efficacy of BCG vaccine formulated in adjuvant is dependent on IL-17A expression","authors":"Steven C. Derrick,&nbsp;Amy Yang,&nbsp;Siobhan Cowley","doi":"10.1016/j.tube.2024.102540","DOIUrl":"10.1016/j.tube.2024.102540","url":null,"abstract":"<div><p>A new, more effective vaccine against tuberculosis (TB) is urgently needed to curtail the current TB problem. The only licensed vaccine, BCG, has been shown to have highly variable protective efficacy in several clinical trials ranging from zero to 80 % against TB disease. We have previously reported that BCG formulated in dimethyl dioctadecyl-ammonium bromide (DDA) with D-(+)-Trehalose 6,6′-Dibehenate (TDB) adjuvant (BCG + Adj) is significantly more protective than BCG alone following murine aerosol <em>Mycobacterium tuberculosis</em> infection. Here we investigate the immunological basis for this improved efficacy by examining expression of different immune markers and cytokines in the lungs of vaccinated mice after <em>M. tuberculosis</em> aerosol challenge. We found significantly greater numbers of pulmonary IL-17A-expressing CD4<sup>+</sup> T cells in mice immunized with BCG+Adj as compared to nonvaccinated and BCG-immunized mice at one-month post-challenge and that the enhanced protection was abrogated in IL-17A-deficient mice. Furthermore, we found significantly higher levels of IL-17A, IL-12p40 and IL-33 expression in the lungs of BCG + Adj immunized animals relative to nonvaccinated mice after <em>M. tuberculosis</em> challenge. These results demonstrate that the DDA/TDB adjuvant increases expression of IL-17A in response to the BCG vaccine and that these augmented IL-17A levels enhance control of <em>M. tuberculosis</em> infection.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102540"},"PeriodicalIF":2.8,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proteome overview of exosome derived from plasma of cows infected with Mycobacterium bovis 从感染了牛分枝杆菌的奶牛血浆中提取的外泌体蛋白质组概览。
IF 2.8 3区 医学
Tuberculosis Pub Date : 2024-07-06 DOI: 10.1016/j.tube.2024.102541
Hangfan Zhou , Wenhui Wu , Qilong Zhang , Tao Zhang , Songhao Jiang , Lei Chang , Yuping Xie , Jiaqiang Zhu , Degang Zhou , Yao Zhang , Ping Xu
{"title":"Proteome overview of exosome derived from plasma of cows infected with Mycobacterium bovis","authors":"Hangfan Zhou ,&nbsp;Wenhui Wu ,&nbsp;Qilong Zhang ,&nbsp;Tao Zhang ,&nbsp;Songhao Jiang ,&nbsp;Lei Chang ,&nbsp;Yuping Xie ,&nbsp;Jiaqiang Zhu ,&nbsp;Degang Zhou ,&nbsp;Yao Zhang ,&nbsp;Ping Xu","doi":"10.1016/j.tube.2024.102541","DOIUrl":"10.1016/j.tube.2024.102541","url":null,"abstract":"<div><p>Bovine tuberculosis (bTB), primarily caused by <em>Mycobacterium bovis</em> (<em>M. bovis</em>), is a globally zoonotic disease with significant economic impacts. Plasma exosomes have been extensively used for investigating disease processes and exploring biomarkers. While mass spectrometry (MS)-based proteomic analysis of plasma exosomes has been employed for human tuberculosis (TB) studies, it has not yet been applied to bTB. Therefore, a comprehensive proteomic overview of plasma exosomes from <em>M. bovis</em>-infected cows is essential. In this study, we presented an extensive proteomic analysis of plasma exosomes from 89 <em>M. bovis</em>-infected cows across three farms, using data dependent acquisition (DDA) mode. Our analysis encompasses 239,894 spectra, 6,011 peptides and 835 proteins. The proteomic overview revealed both consistencies and differences among individual cows, supplements 595 proteins to the bovine exosome library, and enriches tuberculosis and related pathways. Additionally, six pathways were validated as immune response pathways, and three proteins (CATHL1, H1-1, and LCN2) were identified as potential indicators of bTB. This study is the first to investigate the exosome proteome of plasma from cows infected with <em>M. bovis</em>, providing a valuable dataset for exploring candidate bTB markers and understanding the mechanisms of host defense against <em>M. bovis</em>.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102541"},"PeriodicalIF":2.8,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of host immune-related biomarkers in active tuberculosis: A comprehensive analysis of differentially expressed genes 活动性结核病宿主免疫相关生物标志物的鉴定:全面分析差异表达基因
IF 2.8 3区 医学
Tuberculosis Pub Date : 2024-06-28 DOI: 10.1016/j.tube.2024.102538
Alisha Ansari , Gajendra Pratap Singh , Mamtesh Singh , Harpreet Singh
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