{"title":"Constructive appraisal of Zhong et al.’s study on Mycobacterium tuberculosis dormant antigens and PB2-DIMQ vaccine: Opportunities for translational strengthening","authors":"Parth Aphale , Shashank Dokania , Himanshu Shekhar","doi":"10.1016/j.tube.2025.102708","DOIUrl":"10.1016/j.tube.2025.102708","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102708"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565689","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}
Pub Date : 2025-12-01Epub Date: 2025-10-22DOI: 10.1016/j.tube.2025.102702
Angela Hidalgo-Gajardo , Bryan Mangui , Carla Villavicencio , Jorge R. Toledo , Frank Camacho
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), Bacille Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis, but it provides limited and inconsistent protection against pulmonary TB in adults. Furthermore, current diagnostic methods show low sensitivity in latent stages, and the standard treatment is long, complex, and conducive to the emergence of drug-resistant strains.
In this context, heat shock protein X (HspX), also known as Rv2031c or α-crystallin, has emerged as a potential biomarker and vaccine candidate. This 16-kDa protein is predominantly expressed under stressful conditions such as hypoxia and nitric oxide exposure, which are characteristic of the granulomatous microenvironment where MTB persists. Its expression during latency and high immunogenicity has been demonstrated in individuals with latent tuberculosis infection and those vaccinated with BCG.
Preclinical studies have shown that recombinant HspX potentiates the host immune response used as a component in subunit vaccines, either alone or in combination with other antigens. Incorporating this protein into new diagnostic, therapeutic, and vaccine strategies could optimize disease control. This review explores HspX's multifaceted role and potential applications in tuberculosis diagnosis, treatment, and vaccine development.
{"title":"Targeting HspX of Mycobacterium tuberculosis: Advances in diagnostics, treatment, and vaccine development","authors":"Angela Hidalgo-Gajardo , Bryan Mangui , Carla Villavicencio , Jorge R. Toledo , Frank Camacho","doi":"10.1016/j.tube.2025.102702","DOIUrl":"10.1016/j.tube.2025.102702","url":null,"abstract":"<div><div>Tuberculosis (TB) is an infectious disease caused by <em>Mycobacterium tuberculosis</em> (MTB), Bacille Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis, but it provides limited and inconsistent protection against pulmonary TB in adults. Furthermore, current diagnostic methods show low sensitivity in latent stages, and the standard treatment is long, complex, and conducive to the emergence of drug-resistant strains.</div><div>In this context, heat shock protein X (HspX), also known as Rv2031c or α-crystallin, has emerged as a potential biomarker and vaccine candidate. This 16-kDa protein is predominantly expressed under stressful conditions such as hypoxia and nitric oxide exposure, which are characteristic of the granulomatous microenvironment where MTB persists. Its expression during latency and high immunogenicity has been demonstrated in individuals with latent tuberculosis infection and those vaccinated with BCG.</div><div>Preclinical studies have shown that recombinant HspX potentiates the host immune response used as a component in subunit vaccines, either alone or in combination with other antigens. Incorporating this protein into new diagnostic, therapeutic, and vaccine strategies could optimize disease control. This review explores HspX's multifaceted role and potential applications in tuberculosis diagnosis, treatment, and vaccine development.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102702"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423010","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}
Pub Date : 2025-12-01Epub Date: 2025-10-29DOI: 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.
{"title":"In vitro and in vivo efficacy of PI3Kγ inhibitor AS605240 in controlling mycobacterial infections","authors":"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","doi":"10.1016/j.tube.2025.102704","DOIUrl":"10.1016/j.tube.2025.102704","url":null,"abstract":"<div><div>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 <em>M. smegmatis</em> and <em>M. tuberculosis</em> counts in RAW 264.7 cells. Moreover, treatment of <em>M. tuberculosis</em>-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 <em>M. tuberculosis</em>-infected mice. Our data provide novel evidence on the relevance of PI3Kγ as a novel molecular target for new anti-tubercular drugs.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102704"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145424585","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}
Pub Date : 2025-12-01Epub Date: 2025-08-27DOI: 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.
{"title":"A comparative study between milk- and serum-based antibody detection assays for Johne's disease in New Zealand dairy cattle","authors":"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","doi":"10.1016/j.tube.2025.102679","DOIUrl":"10.1016/j.tube.2025.102679","url":null,"abstract":"<div><div>Dairy cattle are affected by Johne's disease. It is caused by <em>Mycobacterium avium</em> subspecies <em>paratuberculosis</em> (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.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102679"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001103","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}
Pub Date : 2025-12-01Epub Date: 2025-09-12DOI: 10.1016/j.tube.2025.102691
Miguel Pinto , Rita Macedo
To improve TB surveillance and diagnosis, the Portuguese National Reference Laboratory (NRL) began implementing whole-genome sequencing (WGS) for all RR/MDR-TB cases in 2019. Since 2020, this approach has been expanded to indiscriminately include all received isolates. We describe the current WGS-based surveillance system in Portugal, framed in prospective and retrospective data (n = 1171), upgraded for antimicrobial resistance (AMR) prediction and epidemiological analysis. This system relies on three main steps: QC/QA and contamination assessment, with a novel data filtering step; genotyping and AMR prediction; and dynamic SNP-based approach, maximizing variable sites under analysis. While lineage 4 was the most prevalent (84.3 %) followed by lineage 2 (9.1 %), less common EU/EEA sub-lineages (e.g., lineages 3 and 6) showcased cross-border transmissions. Molecular clusters (n = 157) displayed distinct AMR profiles and diverse possible epidemiological contexts. Among the pipeline upgrades, we highlight: i) the novel filtering step that allowed the improvement of 123 out of 128 contaminated samples; ii) tolerating missing data per site more than doubled core variable site resolution; iii) automatic maximization of shared variable sites for in-depth cluster analysis, key for consolidating genetic links in epidemiological investigation. This study highlights the importance of sustained prospective genomic surveillance towards strengthening TB management and diagnosis in Portugal.
{"title":"Whole-genome sequencing-based surveillance system for Mycobacterium tuberculosis in Portugal","authors":"Miguel Pinto , Rita Macedo","doi":"10.1016/j.tube.2025.102691","DOIUrl":"10.1016/j.tube.2025.102691","url":null,"abstract":"<div><div>To improve TB surveillance and diagnosis, the Portuguese National Reference Laboratory (NRL) began implementing whole-genome sequencing (WGS) for all RR/MDR-TB cases in 2019. Since 2020, this approach has been expanded to indiscriminately include all received isolates. We describe the current WGS-based surveillance system in Portugal, framed in prospective and retrospective data (n = 1171), upgraded for antimicrobial resistance (AMR) prediction and epidemiological analysis. This system relies on three main steps: QC/QA and contamination assessment, with a novel data filtering step; genotyping and AMR prediction; and dynamic SNP-based approach, maximizing variable sites under analysis. While lineage 4 was the most prevalent (84.3 %) followed by lineage 2 (9.1 %), less common EU/EEA sub-lineages (e.g., lineages 3 and 6) showcased cross-border transmissions. Molecular clusters (n = 157) displayed distinct AMR profiles and diverse possible epidemiological contexts. Among the pipeline upgrades, we highlight: i) the novel filtering step that allowed the improvement of 123 out of 128 contaminated samples; ii) tolerating missing data per site more than doubled core variable site resolution; iii) automatic maximization of shared variable sites for in-depth cluster analysis, key for consolidating genetic links in epidemiological investigation. This study highlights the importance of sustained prospective genomic surveillance towards strengthening TB management and diagnosis in Portugal.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102691"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087616","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}
Pub Date : 2025-12-01Epub Date: 2025-10-04DOI: 10.1016/j.tube.2025.102696
Lei Wang , Li-ping Cheng , Xiao-na Shen , Yuanyuan Yu , Jie Cao , Zhi-bin Liu , Qingrong Qu , Xiao-cui Wu , Wei Sha , Qin Sun
Objective
This study aimed to analyze the differences in lymphocyte subsets and immune function between tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), thereby deepening the understanding of the pathogenesis of these diseases and providing important insights for clinical diagnosis, treatment, and prognosis evaluation.
Methods
Patients with pulmonary imaging abnormalities admitted to the Tuberculosis Department of Shanghai Pulmonary Hospital from January 2023 to December 2023 were included. Based on diagnostic assessments, they were categorized into active tuberculosis (ATB), NTM-PD, and other pulmonary diseases (including inflammatory and neoplastic lung diseases). Flow cytometry was used to detect lymphocyte subset counts.
Results
(1) There were no significant differences in lymphocyte subset counts between the ATB and NTM groups; however, both groups showed marked differences when compared with the group of patients with other respiratory diseases. Specifically, the percentages and absolute counts of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD19+ B cells were significantly lower in the ATB and NTM groups, whereas the levels of CD16+56+ natural killer (NK) cells were higher compared to those with other respiratory diseases.(2) Patients in the non-severe ATB (nSATB) group exhibited higher levels of CD3+ T cells and CD19+ B cells compared to those in the severe ATB (SATB) group.(3) Among patients with ATB, those with concomitant diabetes had lower CD8+ T cell counts and percentages, as well as a higher CD4/CD8 ratio, compared to those without diabetes.(4) In patients with NTM-PD, those with severe disease had lower percentages of CD16+56+ NK cells than those with non-severe NTM-PD.(5) No significant differences in lymphocyte subset parameters were observed between drug-resistant and drug-sensitive ATB patients, or between patients with rapidly growing and slowly growing NTM species.
Conclusion
This study revealed the lymphocyte subset characteristics of patients with TB and NTM infections and identified potential associations between disease severity, diabetes comorbidities, and immune cell subsets with disease status. These findings provide a basis for further research on the immune mechanisms of infectious pulmonary diseases and contribute to the development of precision medicine strategies.
{"title":"Comparative analysis of lymphocyte subsets in tuberculosis, NTM infections, and other respiratory diseases","authors":"Lei Wang , Li-ping Cheng , Xiao-na Shen , Yuanyuan Yu , Jie Cao , Zhi-bin Liu , Qingrong Qu , Xiao-cui Wu , Wei Sha , Qin Sun","doi":"10.1016/j.tube.2025.102696","DOIUrl":"10.1016/j.tube.2025.102696","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to analyze the differences in lymphocyte subsets and immune function between tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), thereby deepening the understanding of the pathogenesis of these diseases and providing important insights for clinical diagnosis, treatment, and prognosis evaluation.</div></div><div><h3>Methods</h3><div>Patients with pulmonary imaging abnormalities admitted to the Tuberculosis Department of Shanghai Pulmonary Hospital from January 2023 to December 2023 were included. Based on diagnostic assessments, they were categorized into active tuberculosis (ATB), NTM-PD, and other pulmonary diseases (including inflammatory and neoplastic lung diseases). Flow cytometry was used to detect lymphocyte subset counts.</div></div><div><h3>Results</h3><div>(1) There were no significant differences in lymphocyte subset counts between the ATB and NTM groups; however, both groups showed marked differences when compared with the group of patients with other respiratory diseases. Specifically, the percentages and absolute counts of CD3<sup>+</sup> T cells, CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, and CD19<sup>+</sup> B cells were significantly lower in the ATB and NTM groups, whereas the levels of CD16<sup>+</sup>56<sup>+</sup> natural killer (NK) cells were higher compared to those with other respiratory diseases.(2) Patients in the non-severe ATB (nSATB) group exhibited higher levels of CD3<sup>+</sup> T cells and CD19<sup>+</sup> B cells compared to those in the severe ATB (SATB) group.(3) Among patients with ATB, those with concomitant diabetes had lower CD8<sup>+</sup> T cell counts and percentages, as well as a higher CD4/CD8 ratio, compared to those without diabetes.(4) In patients with NTM-PD, those with severe disease had lower percentages of CD16<sup>+</sup>56<sup>+</sup> NK cells than those with non-severe NTM-PD.(5) No significant differences in lymphocyte subset parameters were observed between drug-resistant and drug-sensitive ATB patients, or between patients with rapidly growing and slowly growing NTM species.</div></div><div><h3>Conclusion</h3><div>This study revealed the lymphocyte subset characteristics of patients with TB and NTM infections and identified potential associations between disease severity, diabetes comorbidities, and immune cell subsets with disease status. These findings provide a basis for further research on the immune mechanisms of infectious pulmonary diseases and contribute to the development of precision medicine strategies.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102696"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293821","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}
Pub Date : 2025-12-01Epub Date: 2025-09-19DOI: 10.1016/j.tube.2025.102692
Natalia Przysucha , Magdalena Paplińska-Goryca , Katarzyna Górska , Paulina Misiukiewicz-Stępień , Michał Mlącki , Agata Cyran , Rafal Krenke
Background
Chitinases and chitinase-like proteins are implicated in the pathophysiology of lung diseases. This study aimed to evaluate the significance of chitotriosidase (CHIT1) and YKL-40 in tuberculous pleural effusion (TPE), identify their cellular sources, and assess their diagnostic potential as TPE biomarkers.
Methods
This observational, retrospective study included 66 patients with pleural effusion of different origins: malignant (MPE), tuberculous (TPE), parapneumonic (PPE), and transudative (TE). Pleural fluid levels of YKL-40 and CHIT1 were measured. Expressions of YKL-40 and CHIT1 in tuberculous pleural granulomas were also assessed using immunohistochemical staining.
Results
We found the highest median CHIT1 and YKL-40 levels for TPE: 70.51 (interquartile range [IQR] 49.65–136.98) ng/mL and 569.84 (IQR 530.32–706.01) ng/mL, respectively. YKL-40 was significantly higher in TPE than in PPE (387.98 [IQR 262.94–539.09] ng/mL, p < 0.01)] and TE (254.95 [IQR 188.93–334.1 ng/ml] ng/mL, p < 0.001). There was a strong positive correlation between the YKL-40 level in TPE and the percentage of macrophages (r = 0.73, p = 0.003) and the adenosine deaminase activity (r = 0.82, p < 0.001). We revealed strong YKL-40 expression in tuberculoid pleural granulomas.
Conclusion
YKL-40, but not CHIT-1, may contribute to the pleural inflammatory response associated with tuberculosis.
几丁质酶和几丁质酶样蛋白参与肺部疾病的病理生理。本研究旨在评估壳三醇苷酶（CHIT1）和YKL-40在结核性胸腔积液（TPE）中的意义，确定它们的细胞来源，并评估它们作为TPE生物标志物的诊断潜力。方法回顾性观察66例不同来源的胸腔积液：恶性（MPE）、结核性（TPE）、肺副性（PPE）和肺泡性（TE）。测定胸膜液中YKL-40和CHIT1水平。免疫组化染色法检测结核性胸膜肉芽肿组织中YKL-40和CHIT1的表达。结果TPE患者的CHIT1和YKL-40水平中位数最高，分别为70.51（四分位间距[IQR] 49.65 ~ 136.98） ng/mL和569.84 (IQR 530.32 ~ 706.01) ng/mL。TPE中YKL-40含量显著高于PPE （387.98 [IQR 262.94-539.09] ng/mL, p < 0.01）和TE （254.95 [IQR 188.93-334.1] ng/mL, p < 0.001）。TPE中YKL-40水平与巨噬细胞百分比（r = 0.73, p = 0.003）和腺苷脱氨酶活性（r = 0.82, p < 0.001）呈极显著正相关。我们发现YKL-40在结核样胸膜肉芽肿中表达强烈。结论ykl -40可能参与结核相关胸膜炎症反应，而CHIT-1不参与。
{"title":"Exploring CHIT1 and YKL-40 in tuberculous pleural effusion: Insights and implications","authors":"Natalia Przysucha , Magdalena Paplińska-Goryca , Katarzyna Górska , Paulina Misiukiewicz-Stępień , Michał Mlącki , Agata Cyran , Rafal Krenke","doi":"10.1016/j.tube.2025.102692","DOIUrl":"10.1016/j.tube.2025.102692","url":null,"abstract":"<div><h3>Background</h3><div>Chitinases and chitinase-like proteins are implicated in the pathophysiology of lung diseases. This study aimed to evaluate the significance of chitotriosidase (CHIT1) and YKL-40 in tuberculous pleural effusion (TPE), identify their cellular sources, and assess their diagnostic potential as TPE biomarkers.</div></div><div><h3>Methods</h3><div>This observational, retrospective study included 66 patients with pleural effusion of different origins: malignant (MPE), tuberculous (TPE), parapneumonic (PPE), and transudative (TE). Pleural fluid levels of YKL-40 and CHIT1 were measured. Expressions of YKL-40 and CHIT1 in tuberculous pleural granulomas were also assessed using immunohistochemical staining.</div></div><div><h3>Results</h3><div>We found the highest median CHIT1 and YKL-40 levels for TPE: 70.51 (interquartile range [IQR] 49.65–136.98) ng/mL and 569.84 (IQR 530.32–706.01) ng/mL, respectively. YKL-40 was significantly higher in TPE than in PPE (387.98 [IQR 262.94–539.09] ng/mL, p < 0.01)] and TE (254.95 [IQR 188.93–334.1 ng/ml] ng/mL, p < 0.001). There was a strong positive correlation between the YKL-40 level in TPE and the percentage of macrophages (r = 0.73, p = 0.003) and the adenosine deaminase activity (r = 0.82, p < 0.001). We revealed strong YKL-40 expression in tuberculoid pleural granulomas.</div></div><div><h3>Conclusion</h3><div>YKL-40, but not CHIT-1, may contribute to the pleural inflammatory response associated with tuberculosis.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102692"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109023","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}
Pub Date : 2025-12-01Epub Date: 2025-11-19DOI: 10.1016/j.tube.2025.102709
Jason D. Limberis , Alina Nalyvayko , Alexander Mohapatra , Rania Bouzeyen , Zach Howard , Weihao Zheng , John Z. Metcalfe
{"title":"CountFU: Ditching CFUs for qPCR enumeration of Mycobacterium tuberculosis and a call to join the revolution","authors":"Jason D. Limberis , Alina Nalyvayko , Alexander Mohapatra , Rania Bouzeyen , Zach Howard , Weihao Zheng , John Z. Metcalfe","doi":"10.1016/j.tube.2025.102709","DOIUrl":"10.1016/j.tube.2025.102709","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"155 ","pages":"Article 102709"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145576151","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}
Pub Date : 2025-09-01Epub Date: 2025-07-01DOI: 10.1016/j.tube.2025.102672
Thays Maria Costa de Lucena , Débora Elienai de Oliveira Miranda , Juliana Vieira de Barros Arcoverde , Mariana Souza Bezerra Cavalcanti , Willyenne Marilia Dantas , Lindomar José Pena , Virginia Maria Barros de Lorena , Michelle Christiane da Silva Rabello , Jaqueline de Azevedo Silva
Mycobacterium tuberculosis (Mtb) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may induce immunopathology with extensive lung damage in hosts. To elucidate the dynamics of co-infection Mtb and SARS-CoV-2 and its impact on inflammatory mediators’ expression, we conducted a study to evaluate A549, lung epithelial cells, as a potential model for hosting both pathogens simultaneously. Cell infection initiated with Mtb H37Rv and following a 24-h incubation period, the cells were then infected with SARS-CoV-2. After a 72 h incubation period, a precision test was conducted for both pathogens, and total RNA was extracted for subsequent analysis of gene expression by RT-qPCR of the target genes: IFN-γ, TNF-α, IL-6, and IL-1β. Additionally, the levels of IL-1β, IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α in the culture supernatants were measured. A549 cells are a stable and reliable cellular model for co-infection between Mycobacterium tuberculosis and SARS-CoV-2. Co-infection with both pathogens led to downregulation of IFN-γ, TNF-α, and IL-10, and upregulation of IL-6 and IL-1β compared to uninfected cells. A549 cells function as a cellular model for co-infection and seems a good model for elucidating host inflammatory responses in the initial site of infection.
{"title":"Efficient cell model for assessing inflammatory responsive genes in Mycobacterium tuberculosis and SARS-CoV-2 co-infection","authors":"Thays Maria Costa de Lucena , Débora Elienai de Oliveira Miranda , Juliana Vieira de Barros Arcoverde , Mariana Souza Bezerra Cavalcanti , Willyenne Marilia Dantas , Lindomar José Pena , Virginia Maria Barros de Lorena , Michelle Christiane da Silva Rabello , Jaqueline de Azevedo Silva","doi":"10.1016/j.tube.2025.102672","DOIUrl":"10.1016/j.tube.2025.102672","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may induce immunopathology with extensive lung damage in hosts. To elucidate the dynamics of co-infection <em>Mtb</em> and SARS-CoV-2 and its impact on inflammatory mediators’ expression, we conducted a study to evaluate A549, lung epithelial cells, as a potential model for hosting both pathogens simultaneously. Cell infection initiated with <em>Mtb</em> H37Rv and following a 24-h incubation period, the cells were then infected with SARS-CoV-2. After a 72 h incubation period, a precision test was conducted for both pathogens, and total RNA was extracted for subsequent analysis of gene expression by RT-qPCR of the target genes: <em>IFN-γ</em>, <em>TNF-α</em>, <em>IL-6</em>, and <em>IL-1β</em>. Additionally, the levels of IL-1β, IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α in the culture supernatants were measured. A549 cells are a stable and reliable cellular model for co-infection between <em>Mycobacterium tuberculosis</em> and SARS-CoV-2. Co-infection with both pathogens led to downregulation of IFN-γ, TNF-α, and IL-10, and upregulation of IL-6 and IL-1β compared to uninfected cells. A549 cells function as a cellular model for co-infection and seems a good model for elucidating host inflammatory responses in the initial site of infection.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102672"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549310","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}
Non-tuberculous mycobacteria (NTM) are emerging pathogens in human and veterinary medicine, with a globally increasing incidence. In India, sporadic studies have identified an upward trend in NTM infections, but accurate prevalence estimates are lacking due to the absence of nationwide surveillance. Non-tuberculous mycobacteria have been reported in clinically healthy cattle and wildlife globally, complicating tuberculosis (TB) diagnostics and surveillance. This study aimed to characterize NTM species isolated from tissue samples of slaughtered cattle in Chennai using culture and targeted hsp65 gene sequencing. A total of 118 presumed NTM samples from 115 animals were processed, and 49 isolates were confirmed as NTMs by PCR. Sequencing identified 18 different species, with Mycobacterium intracellulare (9/49) being the most frequent, followed by Mycobacterium sp. strain 79_MI18_10584 (6/49) and Mycobacterium elephantis (6/49). Several identified species, including M. intracellulare, M. fortuitum (5/49), M. kansasii (4/49), and M. avium, have caused infections in humans as well. NTMs in cattle lymph nodes without visible lesions suggest their asymptomatic persistence, albeit there being a possibility of transient colonization. Non-tuberculous mycobacteria complicate bovine tuberculosis (bTB) diagnostics by inducing cross-reactive immune responses and forming granulomatous lesions resembling those caused by Mycobacterium tuberculosis complex (MTBC). This study highlights the presence and diversity of NTMs in Indian cattle and emphasizes the need for better surveillance, improved molecular characterization, and better understanding of their epidemiological and immunological roles in both veterinary and public health contexts.
{"title":"Identification of non-tuberculous mycobacteria in slaughtered cattle from Chennai, India","authors":"Harini Ramanujam , Manohar Nesakumar , Kannan Thiruvengadam , Rajaraman Kannan , Sivaraman Palanisamy , Sivakumar Shanmugam , Kannan Palaniyandi","doi":"10.1016/j.tube.2025.102673","DOIUrl":"10.1016/j.tube.2025.102673","url":null,"abstract":"<div><div>Non-tuberculous mycobacteria (NTM) are emerging pathogens in human and veterinary medicine, with a globally increasing incidence. In India, sporadic studies have identified an upward trend in NTM infections, but accurate prevalence estimates are lacking due to the absence of nationwide surveillance. Non-tuberculous mycobacteria have been reported in clinically healthy cattle and wildlife globally, complicating tuberculosis (TB) diagnostics and surveillance. This study aimed to characterize NTM species isolated from tissue samples of slaughtered cattle in Chennai using culture and targeted <em>hsp65</em> gene sequencing. A total of 118 presumed NTM samples from 115 animals were processed, and 49 isolates were confirmed as NTMs by PCR. Sequencing identified 18 different species, with <em>Mycobacterium intracellulare</em> (9/49) being the most frequent, followed by <em>Mycobacterium</em> sp. <em>strain 79_MI18_10584</em> (6/49) and <em>Mycobacterium elephantis</em> (6/49). Several identified species, including <em>M. intracellulare, M. fortuitum</em> (5/49)<em>, M. kansasii</em> (4/49)<em>, and M. avium</em>, have caused infections in humans as well. NTMs in cattle lymph nodes without visible lesions suggest their asymptomatic persistence, albeit there being a possibility of transient colonization. Non-tuberculous mycobacteria complicate bovine tuberculosis (bTB) diagnostics by inducing cross-reactive immune responses and forming granulomatous lesions resembling those caused by <em>Mycobacterium tuberculosis</em> complex (MTBC). This study highlights the presence and diversity of NTMs in Indian cattle and emphasizes the need for better surveillance, improved molecular characterization, and better understanding of their epidemiological and immunological roles in both veterinary and public health contexts.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"154 ","pages":"Article 102673"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722939","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号