Tuberculosis最新文献

{"title":"Assessment of transcriptional markers for the differentiation of Mycobacterium mungi infection status in free-ranging banded mongoose (Mungos mungo)","authors":"Nicholas M. Sybertz ,&nbsp;Shamim Al Jubaer ,&nbsp;Michelle H. Larsen ,&nbsp;Kathleen A. Alexander","doi":"10.1016/j.tube.2024.102565","DOIUrl":"10.1016/j.tube.2024.102565","url":null,"abstract":"<div><p>There is an increasingly urgent need to improve our ability to accurately forecast and control zoonotic diseases in wildlife reservoirs. We are confronted, however, with the continued challenge of accurately determining host infection status across space and time. This dilemma is epitomized with the <em>Mycobacterium tuberculosis</em> Complex (MTBC) pathogens and particularly in free-ranging wildlife, a critical global challenge for both human and animal health. In humans, transcriptional markers have been increasingly identified as a robust tool for diagnosing <em>Mycobacterium tuberculosis</em> (<em>MTB</em>) infection status but have rarely been utilized for diagnosing TB in free-ranging wildlife populations. Here, we report the first use of transcriptional markers to evaluate TB infection status in a free-ranging wildlife species, banded mongoose (<em>Mungos mungo</em>), infected with the MTBC pathogen, <em>Mycobacterium mungi</em>. In this study, we found that <em>GBP5</em> and <em>DUSP3</em> were significantly upregulated in free-ranging banded mongoose infected with <em>M. mungi</em>. These results provide the first step in developing an antemortem diagnostic tool for use in free-ranging wildlife species. Our results highlight the potential of transcriptional marker-based assays to advance our ability to detect and manage TB in free-ranging wildlife, especially in field studies and other scenarios when conventional diagnostics are not feasible.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"149 ","pages":"Article 102565"},"PeriodicalIF":2.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241236","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":"Increasing circulation of multi-drug resistant tuberculosis strains in Buryatia, high-burden and ethnically diverse region in the Russian Far East","authors":"Igor Mokrousov ,&nbsp;Maria Badleeva ,&nbsp;Regina Mudarisova ,&nbsp;Valery Kozhevnikov ,&nbsp;Andrey Markhaev ,&nbsp;Anastasia Guntupova ,&nbsp;Anna Vyazovaya","doi":"10.1016/j.tube.2024.102555","DOIUrl":"10.1016/j.tube.2024.102555","url":null,"abstract":"<div><p>Buryatia is a multidrug-resistant tuberculosis (MDR-TB) high-burden region in the Russian Far East with ethnically diverse population (30 % Mongoloid Buryats and 65 % Russians). Two hundred <em>M. tuberculosis</em> strains from newly-diagnosed patients were subjected to phenotypic testing and genotyping. The Beijing genotype was more prevalent among Russians than Buryats (68 % vs 53 %; P = 0.055). European non-Beijing genotypes (LAM, Ural, Haarlem) were double more prevalent in Buryats vs Russians (39.2 % vs 20.5 %; P = 0.01). Higher prevalence of Beijing among former prison inmates (79 % vs 61 % in other patients, P = 0.1) suggests its increased transmissibility. The Russian epidemic cluster B0/W148 was in 9.5 %, double smaller than elsewhere in Siberia. The hypervirulent Beijing 14717-15-cluster was endemic in Buryatia but paradoxically enough, it was more frequently isolated from Russians than Buryats (9.1 % vs 3.9 %; P = 0.2). Beijing subtypes B0/W148, CAO, and 14717-15 were associated with poly/multi-drug resistance (P = 0.01–0.0001). HIV coinfection was more frequent in Russians than in Buryats: 35/141 (24.8 %) vs 5/51 (9.8 %), P = 0.03. To conclude, <em>M. tuberculosis</em> population structure in Buryatia retained its singularities compared to other parts of Russia and remains strikingly different from the neighboring Mongolia. A circulation of strongly MDR-associated Beijing subtypes and drug-resistant non-Beijing strains highlights a risk of their broader dissemination.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"149 ","pages":"Article 102555"},"PeriodicalIF":2.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146406","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":"Indole triazene compound TU112 demonstrates in vitro activity against dormant Mycobacterium tuberculosis and efficacy against chronic tuberculosis infection in mice","authors":"Margarita O. Shleeva ,&nbsp;Boris V. Nikonenko ,&nbsp;Konstantin B. Majorov ,&nbsp;Pavel Yu Ivanov ,&nbsp;Alexander S. Apt ,&nbsp;Valeria S. Velezheva","doi":"10.1016/j.tube.2024.102556","DOIUrl":"10.1016/j.tube.2024.102556","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"149 ","pages":"Article 102556"},"PeriodicalIF":2.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121903","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":"Detection of Mycobacterium tuberculosis complex in saliva by quantitative PCR: A potential alternative specimen for pulmonary tuberculosis diagnosis","authors":"Sosina Ayalew ,&nbsp;Teklu Wegayehu ,&nbsp;Binium Wondale ,&nbsp;Dawit Kebede ,&nbsp;Mahlet Osman ,&nbsp;Sebsib Niway ,&nbsp;Azeb Tarekegn ,&nbsp;Bamlak Tessema ,&nbsp;Stefan Berg ,&nbsp;Roland T. Ashford ,&nbsp;Adane Mihret","doi":"10.1016/j.tube.2024.102554","DOIUrl":"10.1016/j.tube.2024.102554","url":null,"abstract":"<div><h3>Background</h3><p>Current tuberculosis (TB) diagnostic tests primarily rely on sputum samples, yet many TB patients cannot produce sputum. This study explored whether saliva could be used instead of sputum to diagnose pulmonary TB (PTB).</p></div><div><h3>Method</h3><p>The study included 32 patients with confirmed PTB and 30 patients with other respiratory diseases (ORD). Saliva from all study participants was subjected to quantitative (qPCR) assays targeting the IS<em>1081</em> gene for detection of <em>M. tuberculosis complex</em> DNA.</p></div><div><h3>Results</h3><p>The sensitivity of saliva IS<em>1081</em> qPCR was 65.6 % (95 % CI 48.4–80.2 %) with positive results for 21/32 PTB cases, while the specificity was 96.7 % (95 % CI 85.9–99.6 %) with negative results for 29/30 participants with ORD. Sensitivity improved to 72.4 % (95 % CI 54.6–86.0 %) when sputum-Xpert was used as the reference standard, while remaining similar at 65.5 % (95 % CI 47.4–80.7 %) when culture was used as the reference standard. In receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) for saliva IS<em>1081</em> qPCR was 82.5 % (95 % CI 71.7–93.3 %).</p></div><div><h3>Conclusion</h3><p>Saliva testing offers a promising alternative to sputum for TB diagnosis among confirmed PTB cases. Larger multicenter studies, encompassing diverse clinical TB characteristics, are needed to provide improved estimates of diagnostic sensitivity and specificity.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102554"},"PeriodicalIF":2.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879471","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":"A time-to-event modelling of sputum conversion within two months after antituberculosis initiation among drug-susceptible smear positive pulmonary tuberculosis patients: Implementation of internal and external validation","authors":"Mohd Rahimi Muda ,&nbsp;Orwa Albitar ,&nbsp;Sabariah Noor Harun ,&nbsp;Syed Azhar Syed Sulaiman ,&nbsp;Irfhan Ali Hyder Ali ,&nbsp;Siti Maisharah Sheikh Ghadzi","doi":"10.1016/j.tube.2024.102553","DOIUrl":"10.1016/j.tube.2024.102553","url":null,"abstract":"<div><p>Delayed sputum conversion has been associated with a higher risk of treatment failure or relapse among drug susceptible smear-positive pulmonary tuberculosis patients. Several contributing factors have been identified in many studies, but the results varied across regions and countries. Therefore, the current study aimed to develop a predictive model that explained the factors affecting time to sputum conversion within two months after initiating antituberculosis agents among Malaysian with drug-susceptible smear-positive pulmonary tuberculosis patients. Retrospective data of pulmonary tuberculosis patients followed up at a tertiary hospital in the Northern region of Malaysia from 2013 until 2018 were collected and analysed. Nonlinear mixed-effect modelling software (NONMEM 7.3.0) was used to develop parametric survival models. The final model was further validated using Kaplan-Meier-visual predictive check (KM-VPC) approach, kernel-based hazard rate estimation method and sampling-importance resampling (SIR) method. A total of 224 patients were included in the study, with 34.4 % (77/224) of the patients remained positive at the end of 2 months of the intensive phase. Gompertz hazard function best described the data. The hazard of sputum conversion decreased by 39 % and 33 % for moderate and advanced lesions as compared to minimal baseline of chest X-ray severity, respectively (adjusted hazard ratio (aHR), 0.61; 95 % confidence intervals (95 % CI), (0.44–0.84) and 0.67, 95 % CI (0.53–0.84)). Meanwhile, the hazard also decreased by 59 % (aHR, 0.41; 95 % CI, (0.23–0.73)) and 48 % (aHR, 0.52; 95 % CI, (0.35–0.79)) between active and former drug abusers as compared to non-drug abuser, respectively. The successful development of the internally and externally validated final model allows a better estimation of the time to sputum conversion and provides a better understanding of the relationship with its predictors.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102553"},"PeriodicalIF":2.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879470","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":"A glimpse into the past of Hansen's disease – Re-evaluation and comparative analysis of cases with leprosy from the Avar period of the Trans-Tisza region, Hungary","authors":"Balázs Tihanyi ,&nbsp;Levente Samu ,&nbsp;István Koncz ,&nbsp;Kristóf Hergott ,&nbsp;Pál Medgyesi ,&nbsp;György Pálfi ,&nbsp;Krisztina Ágnes Szabó ,&nbsp;Luca Kis ,&nbsp;Antónia Marcsik ,&nbsp;Erika Molnár ,&nbsp;Olga Spekker","doi":"10.1016/j.tube.2024.102552","DOIUrl":"10.1016/j.tube.2024.102552","url":null,"abstract":"<div><p>Our knowledge of how society viewed leprosy and treated its victims in the past is still scarce, especially in geographical regions and archaeological periods from where no written sources are available. To fill in some research gaps, we provide the comparative analysis of five previously described, probable cases with leprosy from the Avar-period Trans-Tisza region (Hungary). The five skeletons were subject to a detailed macromorphological (re-)evaluation. Where possible, the biological and social consequences of having leprosy were reconstructed based on the observed bony changes and mortuary treatment, respectively. The retrospective, macromorphology-based diagnosis of leprosy could be established in three cases only. Based on the detected skeletal lesions, all of them suffered from near-lepromatous or lepromatous leprosy. The disease resulted in aesthetic repercussions and functional implications, which would have been disadvantageous for these individuals, and limited or changed their possibilities to participate in social situations. They could have even required heavy time investment from their respective communities. The analysis of the mortuary treatment of the confirmed leprosy cases revealed no evidence of a social stigma. These findings indicate that the afflicted have not been systematically expulsed or segregated, at least in death, in the Early Middle Ages of the Carpathian Basin.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102552"},"PeriodicalIF":2.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000787/pdfft?md5=68a1f057b3b4b6cf8b126d76664314ee&pid=1-s2.0-S1472979224000787-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978326","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":"The rv2820c K114N mutation is related with capreomycin tolerance","authors":"Jin-Tian Xu ,&nbsp;Yi Lin ,&nbsp;Tao Cheng ,&nbsp;Jiao-Yu Deng","doi":"10.1016/j.tube.2024.102551","DOIUrl":"10.1016/j.tube.2024.102551","url":null,"abstract":"<div><p>As one of the factors affecting the treatment outcomes, drug tolerance in mycobacteriosis has not been paid due attention. Genome-wide association studies on 607 <em>Mycobacterium tuberculosis</em> clinical isolates with phenotypic drug susceptibility test data revealed that a K114N mutation on the <em>rv2820c</em> gene was highly enriched in capreomycin-resistant isolates (32/213, 15.02%). However, the mutation was also observed in capreomycin-sensitive isolates (10/394, 2.53%). In most cases (31/42, 73.81%), the <em>rv2820c</em> K114N mutation occurred in isolates with the known capreomycin resistance conferring mutation <em>rrs</em> A1401G. In contrast, the general frequency of the <em>rv2820c</em> K114N mutation was low in 7061 genomes downloaded from the National Center for Biotechnology Information database. To determine the impact of this mutation on the antimycobacterial activity of capreomycin, the intact <em>rv2820c</em> gene and the <em>rv2820c</em> K114N mutant were over-expressed in <em>Mycobacterium smegmatis</em> (<em>Ms</em>), and the results of susceptibility tests showed that the <em>rv2820c</em> K114N mutation did not affect the minimum inhibition concentration (MIC) of capreomycin. Subsequently, the data of time-kill assays showed that, it took only 2 h of capreomycin treatment (40 μg/ml, 5 × MIC) to kill 99.9% bacterial cells of <em>Ms</em> MC²155 pMV261::<em>rv2820c</em>_H37Rv, while it took 6 h to achieve that for <em>Ms</em> MC²155 pMV261::<em>rv2820c</em>_K114N. Taken together, these data suggested that the <em>rv2820c</em> K114N mutation is related with capreomycin tolerance, which merits further investigation.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102551"},"PeriodicalIF":2.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845544","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":"Epidemiology and molecular characterization of Mycobacterium tuberculosis including a drug-resistant strain associated with mortality of Asian elephants in Nepal 2019–2022","authors":"Arjun Pandit ,&nbsp;Jeewan Thapa ,&nbsp;Amir Sadaula ,&nbsp;Yasuhiko Suzuki ,&nbsp;Chie Nakajima ,&nbsp;Susan K. Mikota ,&nbsp;Naresh Subedi ,&nbsp;Bijaya Kumar Shrestha ,&nbsp;Michito Shimozuru ,&nbsp;Bhawana Shrestha ,&nbsp;Bijendra Raya ,&nbsp;Sanjay Chaudhary ,&nbsp;Sarad Paudel ,&nbsp;Toshio Tsubota","doi":"10.1016/j.tube.2024.102550","DOIUrl":"10.1016/j.tube.2024.102550","url":null,"abstract":"<div><p>Tuberculosis (TB) is an emerging threat to the survival of elephants in Nepal. We investigated the lung tissue samples from nine elephants that died from 2019 to 2022 in Nepal using culture, conventional PCR, and loop-mediated isothermal amplification (LAMP) and then performed genotyping of five PCR-positive isolates to understand the possible transmission dynamics of <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>). Results showed that two-thirds (6/9) of elephants were confirmed to be infected from <em>Mtb</em> by LAMP, 5/9 by PCR, and 4/9 by culture. Genotyping of <em>Mtb</em> isolates showed that elephants were infected with the Indo-Oceanic and Beijing lineages including an isoniazid-resistant Beijing lineage. MIRU-VNTR-based phylogeny, <em>gyrA,</em> and <em>katG</em> sequencing showed the possibility of ongoing transmission of Indo-Oceanic lineages and likely transmission of the drug-resistant Beijing lineage from human to elephant. Implementation of comprehensive surveillance and preventive measures are urgently needed to address this zoonotic disease and protect elephants from TB in Nepal.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102550"},"PeriodicalIF":2.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141842081","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":"Detection of Mycobacterium tuberculosis transrenal DNA in urine samples among adults in Peru","authors":"Annelies W. Mesman ,&nbsp;Roger I. Calderon ,&nbsp;Laura Hauns ,&nbsp;Nira R. Pollock ,&nbsp;Milagros Mendoza ,&nbsp;Rebecca C. Holmberg ,&nbsp;Molly F. Franke","doi":"10.1016/j.tube.2024.102549","DOIUrl":"10.1016/j.tube.2024.102549","url":null,"abstract":"<div><p>Diagnosis of pulmonary tuberculosis (TB) relies on a sputum sample, which cannot be obtained from all symptomatic individuals. <em>Mycobacterium tuberculosis (Mtb)</em> transrenal DNA (trDNA) has been detected in urine, an easily obtainable, noninvasive, alternative sample type. However, reported sensitivities have been variable and likely depend on collection and assay procedures and aspects of trDNA biology. We analyzed three serial urine samples from each of 75 adults with culture-confirmed pulmonary TB disease in Lima, Peru for detection of trDNA using short-fragment real-time PCR. Additionally, we examined host, urine, and sampling factors associated with detection. Overall per-sample sensitivity was 38 % (95 % Confidence Interval [CI] 30–45 %). On an individual level (i.e., any of the three samples positive), sensitivity was 73 % (95 % CI: 62–83 %). Sensitivity was highest among samples from patients with smear-positive TB, 92 % (95 % CI: 62–100 %). Specificity from a single sample from each of 10 healthy controls was 100 % (95 % CI: 69–100 %). Adjusting our assay positivity threshold increased individual-level sensitivity to 88 % (95 % CI: 78–94 %) overall without affecting the specificity. We did not find associations between <em>Mtb</em> trDNA detection and individual characteristics or urine sample characteristics. Overall, our results support the potential of trDNA detection for TB diagnosis.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102549"},"PeriodicalIF":2.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000751/pdfft?md5=b29c2b797b3ffd1bc9783e0e65c2b591&pid=1-s2.0-S1472979224000751-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890222","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":"Metformin modulates corticosteroids hormones in adrenals cells promoting Mycobacterium tuberculosis elimination in human macrophages","authors":"Oscar E. Gonzalez-Muñiz ,&nbsp;Adrián Rodriguez-Carlos ,&nbsp;Alan Santos-Mena ,&nbsp;Yolanda M. Jacobo-Delgado ,&nbsp;Irma Gonzalez-Curiel ,&nbsp;Cesar Rivas-Santiago ,&nbsp;Gabriela Navarro-Tovar ,&nbsp;Bruno Rivas-Santiago","doi":"10.1016/j.tube.2024.102548","DOIUrl":"10.1016/j.tube.2024.102548","url":null,"abstract":"<div><p>Research suggests that both tuberculosis (TB) and type 2 diabetes mellitus (T2DM) have an immuno-endocrine imbalance characterized by dysregulated proinflammatory molecules and hormone levels (high cortisol/DHEA ratio), impeding an effective immune response against <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) driven by cytokines, antimicrobial peptides (AMPs), and androgens like DHEA. Insulin, sulfonylurea derivatives, and metformin are commonly used glucose-lowering drugs in patients suffering from TB and T2DM. For this comorbidity, metformin is an attractive target to restore the immunoendocrine mechanisms dysregulated against <em>Mtb</em>. This study aimed to assess whether metformin influences cortisol and DHEA synthesis in adrenal cells and if these hormones influence the expression of proinflammatory cytokines and AMPs in <em>Mtb</em>-infected macrophages. Our results suggest that metformin may enhance DHEA synthesis while maintaining cortisol homeostasis. In addition, supernatants from metformin-treated adrenal cells decreased mycobacterial loads in macrophages, which related to rising proinflammatory cytokines and AMP expression (HBD-2 and 3). Intriguingly, we find that HBD-3 and LL-37 can modulate steroid synthesis in adrenal cells with diminished levels of cortisol and DHEA, highlighting the importance of crosstalk communication between adrenal hormones and these effectors of innate immunity. We suggest that metformin's effects can promote innate immunity against Mtb straight or through modulation of corticosteroid hormones.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"148 ","pages":"Article 102548"},"PeriodicalIF":2.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789149","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}