Tuberculosis最新文献

{"title":"Steroid immune responsive gene regulation in Mycobacterium tuberculosis infection in vitro","authors":"Maria Eduarda de Albuquerque Borborema ,&nbsp;Débora Elienai de Oliveira Miranda ,&nbsp;Thays Maria Costa de Lucena ,&nbsp;Virgínia Maria Barros de Lorena ,&nbsp;Michelle Christiane da Silva Rabello ,&nbsp;Jaqueline de Azevêdo Silva","doi":"10.1016/j.tube.2024.102497","DOIUrl":"10.1016/j.tube.2024.102497","url":null,"abstract":"<div><p>Tuberculosis (TB) is an infectious disease displaying a multifactorial pathology. The immunomodulatory role attributed to steroid hormones, such as vitamin D₃ (VD₃) and 17β-estradiol (E₂), highlighted the importance of these hormones against <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) infection. In order to understand their influence upon gene expression of immune and inflammatory responsive genes against <em>Mtb</em> we tested it <em>in vitro</em> using peripheral blood mononuclear cells (PBMCs). Cells were pretreated with VD₃ (50 ng/mL) or E₂ (100 nM/mL) and co-cultured with <em>H37Rv Mtb</em> or stimulated with lipopolysaccharide from <em>Escherichia coli</em> (LPS). After 24 h and 72 h of co-culture the <em>Mtb</em> viability in macrophages test was performed, as well the total RNA isolation for gene expression analysis by RT-qPCR of the following target genes: <em>NLRP3</em>, <em>DC-SIGN</em>, <em>IL-1β</em>, and <em>IL-10</em>. We also measured IL-10, TNF, IFN-γ, IL-4, IL-6, and IL-2 supernatant levels. As the main results, we found that VD₃ and E₂ downregulated the expression of inflammatory genes <em>NLRP3</em>, <em>IL-1β,</em> and <em>IL-10</em> expression in <em>Mtb</em> co-cultured cells. Finally, VD₃ treatment increased the release of the cytokine IFN-γ in <em>Mtb-</em>infected cells, while E₂ treatment inhibited the release of IL-10, TNF, IFN-γ, and IL-6. Therefore, we report an immunogenetic influence of VD₃ and E₂ upon <em>Mtb</em> co-culture.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102497"},"PeriodicalIF":3.2,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919976","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}

{"title":"Analysis of T-lymphocyte subsets and risk factors in children with tuberculosis","authors":"Wei-Wei Ma ,&nbsp;Ling-Chao Wang ,&nbsp;De-An Zhao ,&nbsp;Na Wei ,&nbsp;Jun-Wei Cui ,&nbsp;Shu-Jun Li","doi":"10.1016/j.tube.2024.102496","DOIUrl":"10.1016/j.tube.2024.102496","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Tuberculosis (TB) is not only related to infection but also involves immune factors. This study explores the changes in T-lymphocyte subsets in children with TB who are human immunodeficiency virus (HIV)-negative and examines their relationship using chest computed tomography (CT) scans. Additionally, the study identifies risk factors for severe TB (STB) in children and establishes relevant risk prediction models.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;We recruited 235 participants between 2018 and 2022, comprising 176 paediatric patients with TB who were HIV-negative and 59 age-matched children with bacterial community-acquired pneumonia (CAP). We quantitatively analysed and compared T-lymphocyte subsets between the two groups and among different types of TB infection. Both univariate and multivariate analyses of clinical and laboratory characteristics were conducted to identify independent risk factors for STB in children and to establish a risk prediction model.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The absolute counts of CD3, CD4 and CD8 T-cells in children with TB infection decreased significantly compared with bacterial CAP. The percentage of CD8 T-cells increased, whereas the percentage of CD4 T-cells did not change significantly. The absolute count of CD3, CD4 and CD8 T-cells in extrapulmonary TB (EPTB) was significantly higher than in extra-respiratory TB, with unchanged subset percentages. According to chest CT lesion classification, CD4 T-cell counts decreased significantly in S3 compared with S1 or S2, with no significant change in CD3 and CD8 T-cell counts and percentages. No significant differences were observed in lymphocyte subset counts and percentages between S1 and S2. Univariate analyses indicated that factors such as age, symptom duration, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate, prealbumin level, albumin level, globulin level, albumin/globulin (A/G) ratio, high-sensitivity C-reactive protein (Hs-CRP) level and CD4 and CD8 T-cell counts are associated with STB. Multivariate logistic regression analysis revealed that age, Hs-CRP level, NLR, symptom duration and A/G ratio are independent risk factors for STB in children. Increased age, Hs-CRP levels and NLR, along with decreased A/G, correlate with increased susceptibility to STB. A nomogram model, based on these independent risk factors, demonstrated an area under the receiver operating characteristics curve of 0.867 (95% CI: 0.813–0.921). Internal verification confirmed the model's accuracy, with the calibration curve approaching the ideal and the Hosmer–Lemeshow goodness-of-fit test showing consistent results (χ&lt;sup&gt;2&lt;/sup&gt; = 12.212, p = 0.142).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;In paediatric patients with TB, the absolute counts of all lymphocyte subsets were considerably reduced compared with those in patients with bacterial CAP. Clinicians should consider the possibility of EPTB infecti","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102496"},"PeriodicalIF":3.2,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000222/pdfft?md5=d9f92cecb2ef90ab4b025bcead611fc8&pid=1-s2.0-S1472979224000222-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139920177","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}

{"title":"Demonstrating the utility of the ex vivo murine mycobacterial growth inhibition assay (MGIA) for high-throughput screening of tuberculosis vaccine candidates against multiple Mycobacterium tuberculosis complex strains","authors":"Hannah Painter ,&nbsp;Sam Willcocks ,&nbsp;Andrea Zelmer ,&nbsp;Rajko Reljic ,&nbsp;Rachel Tanner ,&nbsp;Helen Fletcher","doi":"10.1016/j.tube.2024.102494","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102494","url":null,"abstract":"<div><p>Human tuberculosis (TB) is caused by various members of the <em>Mycobacterium tuberculosis</em> (Mtb) complex. Differences in host response to infection have been reported, illustrative of a need to evaluate efficacy of novel vaccine candidates against multiple strains in preclinical studies. We previously showed that the murine lung and spleen direct mycobacterial growth inhibition assay (MGIA) can be used to assess control of <em>ex vivo</em> mycobacterial growth by host cells. The number of mice required for the assay is significantly lower than <em>in vivo</em> studies, facilitating testing of multiple strains and/or the incorporation of other cellular analyses. Here, we provide proof-of-concept that the murine MGIA can be applied to evaluate vaccine-induced protection against multiple Mtb clinical isolates. Using an ancient and modern strain of the Mtb complex, we demonstrate that <em>ex vivo</em> bacillus Calmette–Guérin (BCG)-mediated mycobacterial growth inhibition recapitulates protection observed in the lung and spleen following <em>in vivo</em> infection of mice. Further, we provide the first report of cellular and transcriptional correlates of BCG-induced growth inhibition in the lung MGIA. The <em>ex vivo</em> MGIA represents a promising platform to gain early insight into vaccine performance against a collection of Mtb strains and improve preclinical evaluation of TB vaccine candidates.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102494"},"PeriodicalIF":3.2,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000209/pdfft?md5=3a411230d0757059acf5f7d8ee705a37&pid=1-s2.0-S1472979224000209-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139749264","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}

{"title":"Caveolin-1 affects early mycobacterial infection and apoptosis in macrophages and mice","authors":"Yuqing Wu ,&nbsp;Andrea Riehle ,&nbsp;Barbara Pollmeier ,&nbsp;Stephanie Kadow ,&nbsp;Fabian Schumacher ,&nbsp;Marek Drab ,&nbsp;Burkhard Kleuser ,&nbsp;Erich Gulbins ,&nbsp;Heike Grassmé","doi":"10.1016/j.tube.2024.102493","DOIUrl":"10.1016/j.tube.2024.102493","url":null,"abstract":"<div><p>Tuberculosis, caused by <em>Mycobacterium tuberculosis</em>, remains one of the deadliest infections in humans. Because <em>Mycobacterium bovis</em> Bacillus Calmette-Guérin (BCG) share genetic similarities with <em>Mycobacterium tuberculosis</em>, it is often used as a model to elucidate the molecular mechanisms of more severe tuberculosis infection. Caveolin-1 has been implied in many physiological processes and diseases, but it's role in mycobacterial infections has barely been studied. We isolated macrophages from Wildtype or Caveolin-1 deficient mice and analyzed hallmarks of infection, such as internalization, induction of autophagy and apoptosis. For <em>in vivo</em> assays we intravenously injected mice with BCG and investigated tissues for bacterial load with colony-forming unit assays, bioactive lipids with mass spectrometry and changes of protein expressions by Western blotting. Our results revealed that Caveolin-1 was important for early killing of BCG infection <em>in vivo</em> and <em>in vitro</em>, controlled acid sphingomyelinase (Asm)-dependent ceramide formation, apoptosis and inflammatory cytokines upon infection with BCG. In accordance, Caveolin-1 deficient mice and macrophages showed higher bacterial burdens in the livers. The findings indicate that Caveolin-1 plays a role in infection of mice and murine macrophages with BCG, by controlling cellular apoptosis and inflammatory host response. These clues might be useful in the fight against tuberculosis.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"147 ","pages":"Article 102493"},"PeriodicalIF":3.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000192/pdfft?md5=a28ccebedc8d781a4e2dfdaa37da06ff&pid=1-s2.0-S1472979224000192-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139882544","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}

{"title":"Transmission of drug-resistant Mycobacterium tuberculosis isolates between Finnish- and foreign-born cases, 2014–2021: A molecular epidemiological study","authors":"Jiahui Zhu ,&nbsp;Marjo Haanpera ,&nbsp;Silja Mentula ,&nbsp;Olli Vapalahti ,&nbsp;Hanna Soini ,&nbsp;Tarja Sironen ,&nbsp;Ravi Kant ,&nbsp;Fathiah Zakham","doi":"10.1016/j.tube.2024.102492","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102492","url":null,"abstract":"<div><h3>Background</h3><p>Data on the molecular epidemiology and transmission of drug-resistant <em>Mycobacterium tuberculosis</em> (MTB) in low-incidence settings with immigration from high-incidence settings is limited.</p></div><div><h3>Method</h3><p>We included 115 drug-resistant (DR) MTB isolates with whole-genome sequencing data isolated in Finland between 2014 and 2021. Potential transmission clusters were identified using a threshold of 12 single-nucleotide polymorphisms (SNPs). Highly related clusters were identified using a threshold of 5 SNPs.</p></div><div><h3>Result</h3><p>Of the 115 DR MTB isolates, 31 (27.0%) isolates were from Finnish-born cases and 84 (73.0%) were from foreign-born cases. The proportion of multidrug-resistant (MDR) MTB isolates (30/84, 35.7%) from foreign-born cases was higher than that of MDR MTB isolates from Finnish-born cases (8/31, 25.8%). Lineage 2 (40/115, 34.8%) and lineage 4 (40/115, 34.8%) were the most prevalent lineages. A total of 25 (21.7%) isolates were classified into eight potential transmission clusters (≤12 SNPs). Furthermore, five highly related clusters (≤5 SNPs) were identified, including three DR MTB isolates from Finnish-born cases and 14 DR isolates from foreign-born cases.</p></div><div><h3>Conclusion</h3><p>The risk of DR MTB transmission between Finnish- and foreign-born persons is not negligible. Further research on clustering analysis in drug-susceptible MTB is worth to inform tuberculosis management and control in low-incidence settings with increasing immigration.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102492"},"PeriodicalIF":3.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000180/pdfft?md5=59447be64e2ef863c826da394eb7ac1e&pid=1-s2.0-S1472979224000180-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139744237","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}

{"title":"Efficacies of three drug regimens containing omadacycline to treat Mycobacteroides abscessus disease","authors":"Binayak Rimal ,&nbsp;Chandra M. Panthi ,&nbsp;Yi Xie ,&nbsp;Daniel C. Belz ,&nbsp;Elisa H. Ignatius ,&nbsp;Christopher K. Lippincott ,&nbsp;Daniel H. Deck ,&nbsp;Alisa W. Serio ,&nbsp;Gyanu Lamichhane","doi":"10.1016/j.tube.2024.102482","DOIUrl":"https://doi.org/10.1016/j.tube.2024.102482","url":null,"abstract":"<div><p><em>Mycobacteroides abscessus</em> (<em>Mab,</em> also known as <em>Mycobacterium abscessus</em>) causes opportunistic pulmonary and soft tissue infections that are difficult to cure with existing treatments. Omadacycline, a new tetracycline antibiotic, exhibits potent <em>in vitro</em> and <em>in vivo</em> activity against <em>Mab</em>. As regimens containing multiple antibiotics are required to produce a durable cure for <em>Mab</em> disease, we assessed efficacies of three three-drug combinations in a pre-clinical mouse model of pulmonary <em>Mab</em> disease to identify companion drugs with which omadacycline exhibits the highest efficacy. Additionally, we assessed the susceptibility of <em>Mab</em> recovered from mouse lungs after four weeks of exposure to the three triple-drug regimens. Among the three-drug regimens, omadacycline + imipenem + amikacin produced the largest reduction in <em>Mab</em> burden, whereas omadacycline + imipenem + linezolid exhibited the most effective early bactericidal activity. Omadacycline + linezolid + clofazimine, a regimen that can be administered orally, lacked early bactericidal activity but produced a gradual reduction in the lung <em>Mab</em> burden over time. The robust efficacy exhibited by these three regimens in the mouse model supports their further evaluation in patients with <em>Mab</em> lung disease. As we were unable to isolate drug-resistant <em>Mab</em> mutants at the completion of four weeks of treatment, these triple-drug combinations show promise of producing durable cure and minimizing selection of resistant mutants.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102482"},"PeriodicalIF":3.2,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000088/pdfft?md5=386b6f32525281577510225b87d29728&pid=1-s2.0-S1472979224000088-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139744238","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}

{"title":"Corrigendum to “Quantitative proteomics reveals plasma protein profile and potential pathways in pulmonary tuberculosis patients with and without diabetes” [Tuberculosis 143 (2023) 102424]","authors":"Xinxin He ,&nbsp;Yunguang Wang ,&nbsp;Yue Yang ,&nbsp;Qiang He ,&nbsp;Lifang Sun ,&nbsp;Juan Jin","doi":"10.1016/j.tube.2024.102481","DOIUrl":"10.1016/j.tube.2024.102481","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"146 ","pages":"Article 102481"},"PeriodicalIF":3.2,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000076/pdfft?md5=2955bfccfbe165c5c7d79146cfbbd789&pid=1-s2.0-S1472979224000076-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139661463","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}

{"title":"Diagnosing osteoarticular tuberculosis and detecting rifampicin resistance: A comparative analysis of Truenat MTB Plus vs GeneXpert Ultra","authors":"Kusum Sharma ,&nbsp;Megha Sharma ,&nbsp;Aman Sharma ,&nbsp;Mandeep Singh Dhillon","doi":"10.1016/j.tube.2024.102483","DOIUrl":"10.1016/j.tube.2024.102483","url":null,"abstract":"<div><h3>Setting</h3><p><span>Diagnosing osteoarticular tuberculosis (OATB) and detecting </span>drug resistance is a challenge in an endemic country like India.</p></div><div><h3>Objective</h3><p>Truenat MTB Plus assay (TruPlus), a chip-based portable machine, was compared with GeneXpert Ultra (GxUltra) for diagnosing drug-resistant OATB.</p></div><div><h3>Design</h3><p><span>115 synovial fluid and pus specimens [22 culture-positive confirmed, 58 culture-negative clinically-suspected, 35 non-TB controls] processed between 2017 and 2023 were subjected to TruPlus, GxUltra and multiplex-PCR for diagnosing OATB. They were further screened for </span>rifampicin resistance using TruRif chip. The performance was evaluated against composite reference standard, phenotypic drug susceptibility testing and rpoB gene sequencing.</p></div><div><h3>Results</h3><p>TruPlus, GxUltra and MPCR detected 77.5 %, 71.25 %, and 83.75 %, cases of OATB, respectively. TruPlus detected five additional cases missed by GxUltra. The performance of TruPlus was comparable to GxUltra (p = 0.074) and to MPCR (p = 0.074), while performance of GxUltra was significantly inferior to MPCR (p = 0.004). The overall agreement with reference standard was substantial for TruPlus and MPCR and moderate for GxUltra. Both TruRif and GxUltra reported 4 cases as rifampicin resistant.</p></div><div><h3>Conclusion</h3><p>TruPlus along with TruRif offers better sensitivity than GxUltra. Its compact and portable platform allows wider application in peripheral settings, thus making it a pragmatic solution for diagnosing OATB and its drug resistance.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"145 ","pages":"Article 102483"},"PeriodicalIF":3.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139661211","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}

{"title":"Construction and expression of Mycobacterium tuberculosis fusion protein SHR3 and its immunogenicity analysis in combination with various adjuvants","authors":"Zian Zhang ,&nbsp;Lifa Xu ,&nbsp;Xiaochun Wang ,&nbsp;LingYun Kong ,&nbsp;Zilun Shi ,&nbsp;Qiangsen Zhong ,&nbsp;Yun Xu ,&nbsp;Jianghong Wang","doi":"10.1016/j.tube.2024.102480","DOIUrl":"10.1016/j.tube.2024.102480","url":null,"abstract":"<div><p><span><span>Tuberculosis (TB) today remains the leading cause of global deaths due to infectious bacterial pathogens<span><span>. The Bacillus Calmette-Guérin (BCG) vaccine is the only vaccine clinically used to prevent TB. However, its limitations in preventing latent infection and TB reactivation mean that it does not provide comprehensive protection. In this study, we successfully constructed and expressed the multistage fusion protein, SHR3, and used whole blood IFN-γ </span>release assay (WBIA) with flow cytometry to detect </span></span>antigen specificity, further confirmed by enzyme-linked immunosorbent assay (ELISA). SHR3 and its subfractional proteins stimulated the level of IFN-γ production by lymphocytes from M. tb-infected patients, inducing the production of single-positive and double-positive CD4</span>⁺ and CD8⁺<span><span> T cells<span> with IFN-γ and IL-2, at levels significantly higher than those of healthy controls. The fusion protein and complex adjuvant group (SHR3/DMT) induced mice to produce significantly higher levels of </span></span>IgG antibodies<span><span> and their subclasses, with IgG2a/IgG1 results showing a convergent Th1-type response; mice in the BCG + SHR3/DMT group induced secretion of the highest levels of IL-2, and TNF-α, irrespective of stimulation with </span>purified protein derivative<span> or SHR3. These findings suggest that SHR3/DMT could be a potential subunit vaccine<span> candidate that may serve as an effective booster vaccine after BCG primary immunization.</span></span></span></span></p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"145 ","pages":"Article 102480"},"PeriodicalIF":3.2,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139556397","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}

{"title":"The use of Mycobacterium tuberculosis H37Ra-infected immunocompetent mice as an in vivo model of persisters","authors":"Neetu Kumari ,&nbsp;Romil Sharma ,&nbsp;Juned Ali ,&nbsp;Gyan Chandra ,&nbsp;Sarika Singh ,&nbsp;Manju Y. Krishnan","doi":"10.1016/j.tube.2024.102479","DOIUrl":"10.1016/j.tube.2024.102479","url":null,"abstract":"<div><p>Persistence of <span><em>Mycobacterium tuberculosis</em></span><span><span><span> (Mtb) is one of the challenges to successful treatment of tuberculosis (TB). In vitro models of non-replicating Mtb are used to test the efficacy of new molecules against Mtb persisters. The H37Ra strain is attenuated for growth in macrophages and </span>mice. We validated H37Ra-infected immunocompetent mice for testing anti-TB molecules against slow/non-replicating Mtb in vivo. Swiss mice were infected intravenously with H37Ra and monitored for </span>CFU<span> burden and histopathology for a period of 12 weeks. The bacteria multiplied at a slow pace reaching a maximum load of ∼10</span></span>⁶ in 8–12 weeks depending on the infection dose, accompanied by time and dose-dependent histopathological changes in the lungs. Surprisingly, four-weeks of treatment with isoniazid-rifampicin-ethambutol-pyrazinamide combination caused only 0.4 log₁₀ and 1 log₁₀<span><span><span> reduction in CFUs in lungs and spleen respectively. The results show that ∼40 % of the H37Ra bacilli in lungs are persisters after 4 weeks of anti-TB therapy. Isoniazid/rifampicin </span>monotherapy also showed similar results. A combination of </span>bedaquiline and isoniazid reduced the CFU counts to &lt;200 (limit of detection), compared to ∼5000 CFUs by isoniazid alone. The study demonstrates an in vivo model of Mtb persisters for testing new leads using a BSL-2 strain.</span></p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"145 ","pages":"Article 102479"},"PeriodicalIF":3.2,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139499793","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}