Tuberculosis最新文献

{"title":"A fusion protein LT25 containing Rv2660c failed to provide protection against Mycobacterium bovis infection due to limited humoral immune responses.","authors":"Yuqi Liu, Juan Wang, Tianli Yao, Dandan Chen, Yahong Wang, Fei Li, Bingdong Zhu","doi":"10.1016/j.tube.2026.102771","DOIUrl":"https://doi.org/10.1016/j.tube.2026.102771","url":null,"abstract":"<p><p>Rv2660c is present in both Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis) and has been reported as a protective antigen. In this study, Rv2660c was linked with another M. tuberculosis specific antigen Rv2645, which is present in M. tuberculosis but not in M. bovis, to construct a fusion protein Rv2645-Rv2660c (LT25 in short). LT25 failed to confer protection following M. bovis challenge. Structural predictions via AlphaFold 3 revealed that LT25 retained the native conformation of Rv2645, whereas Rv2660c underwent significant conformational alterations. LT25 elicited strong Rv2645 and Rv2660c-specific cellular immune responses and high levels of Rv2645-specific antibodies, but lower levels of Rv2660c-specific antibodies than Rv2660c did. Further investigation showed that the Rv2660c-induced polyclonal antibody possessed stronger phagocytosis-promoting activity than LT25-induced antibodies did. These findings suggest that the structural integrity of Rv2660c is essential for its protective function.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"159 ","pages":"102771"},"PeriodicalIF":2.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843282","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":"Demonstration of extracellular traps in tuberculous pleural effusion from adult patients.","authors":"Geeta Lal, Manisha Dass, Neha Jindal, Ritu Singhal, Manpreet Bhalla, Ashutosh Nath Aggarwal, Sagarika Haldar","doi":"10.1016/j.tube.2026.102763","DOIUrl":"https://doi.org/10.1016/j.tube.2026.102763","url":null,"abstract":"<p><p>In pleural tuberculosis (TB), pleural effusion is typically characterized by a lymphocytic-rich exudate; however, neutrophils and macrophages predominate during the initial phase of infection. These immune cells are known to combat pathogens via phagocytosis, degranulation, and formation of extracellular traps (ETs)-a recently recognized defence mechanism. Although in-vitro and in-vivo studies have demonstrated ETs formation during Mycobacterium tuberculosis infection, their presence in clinical samples of patients with pleural TB has not been previously demonstrated. In this study, we employed multiple methods to demonstrate the presence of ETs in tuberculous pleural effusion (TPE) from patients with confirmed TB (Xpert MTB/RIF-positive/culture-positive/pleural biopsy Ziehl-Neelsen-stainingacid fast bacilli-positive). Immunofluorescence microscopy revealed DNA co-localized with ET markers like myeloperoxidase, neutrophil elastase, and citrullinated histones-confirming ETs in TPE samples, and this was further supported by immunoblotting. Proteomic analysis of TPE samples revealed the presence of key ET-associated proteins, including histones, myeloperoxidase, matrix metalloproteinase-9, and the S100A8/A9 complex. Protein-protein interaction and gene ontology analyses revealed that these proteins are involved in ET-related biological processes, such as neutrophil degranulation and collagen degradation. To the best of our knowledge, this is the first clinical evidence of ETs in TPE, suggesting a potential role in the immunopathogenesis of pleural TB.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"159 ","pages":"102763"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821253","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":"Novel plasma biomarkers for the diagnosis of pulmonary tuberculosis","authors":"Camila P. Sobrinho ,&nbsp;Luana E. Araújo ,&nbsp;Rodrigo L. Meira ,&nbsp;Thainá Horta ,&nbsp;Silvania Cerqueira ,&nbsp;Flávia Marília Fonseca Oliveira ,&nbsp;Jéssica Petrilli ,&nbsp;Sérgio Arruda ,&nbsp;Adriano Queiroz","doi":"10.1016/j.tube.2026.102733","DOIUrl":"10.1016/j.tube.2026.102733","url":null,"abstract":"<div><div>The World Health Organization (WHO) has highlighted the need for new diagnostic tests for pulmonary tuberculosis (TB) that use easily obtainable samples, such as blood, to provide rapid and affordable results suitable for primary healthcare settings. To address this, we evaluated the diagnostic potential of 34 markers quantified by Luminex in supernatants of whole-blood cultures, either stimulated or not with an apolar lipid extract from <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>). The study included 20 patients with pulmonary TB and 20 symptomatic respiratory (SR) non-TB individuals. In unstimulated cultures, eight biomarkers (IL-18, IL-1RA, IL-1β, IL-8, IP-10, MIP-1β, SDF-1α, and TNF-α) differentiated TB patients from SR - non-TB patients, with areas under the ROC curve (AUC) ranging from 0.71 to 0.82. Combinatorial analyses with four-marker panels, namely, IL-18 + IL-1β, IL-1RA + IL-18, IL-18 + IL-1β + IL-1RA and IL-18 + IL-1β + IL-1RA + MIP-1β, revealed AUCs of 0.84–0.90, specificities above 90 % and sensitivities between 70 % and 75 %. The addition of the lipid extract to the whole-blood culture did not improve the discriminatory power of the panels. Validation of the IL-1RA + IL-18 combination by ELISA in an independent group (21 TB patients and 33 SR patients) yielded an AUC of 0.76, a sensitivity of 62 %, a specificity of 88 %, and an accuracy of 78 %. The collective elevation of these cytokines suggests an interplay between pro- and anti-inflammatory pathways in the host response. Although the selected biomarker panels showed moderate diagnostic performance in the ELISA test, other combinations may be useful in helping to predict TB progression or monitor treatment outcomes.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102733"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929115","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":"Proteomic insights into the adaptation of Mycobacterium bovis to hypoxic conditions","authors":"María Mercedes Bigi ,&nbsp;Magdalena Portela ,&nbsp;Laura Inés Klepp ,&nbsp;Elizabeth Andrea García ,&nbsp;Qi Zhang ,&nbsp;Sen Wang ,&nbsp;Jinlong Bei ,&nbsp;Rosario Durán ,&nbsp;Fabiana Bigi","doi":"10.1016/j.tube.2026.102739","DOIUrl":"10.1016/j.tube.2026.102739","url":null,"abstract":"<div><div>Bovine tuberculosis (bTB) is an important cattle disease with major public health and economic impacts. <em>Mycobacterium bovis</em>, its causative agent, is thought to persist in non-replicative forms within the host, similar to <em>Mycobacterium tuberculosis</em>, leading to chronic or latent infection. In this study, we used the Wayne model—an in vitro system that gradually depletes oxygen—to mimic the hypoxic conditions <em>M. bovis</em> may encounter during latency. Growth analysis showed that part of the bacterial culture remained viable but non-replicative under hypoxia, while another fraction likely lysed, as indicated by declining optical density during late hypoxia and reduced colony-forming units.</div><div>Secreted proteome analysis identified 36 proteins detected exclusively in culture supernatants, with Cut3, SapM, and Cdh accumulating more under hypoxia (p &lt; 0.05, FDR = 0.25). In the cellular proteome, 288 proteins showed differential accumulation (p &lt; 0.05, FDR = 0.25), with 172 more abundant under hypoxia. Under oxygen depletion, <em>M. bovis</em> increased proteins related to nitrogen and lipid metabolism, purine biosynthesis, carbon metabolism, anaplerotic pathways, and several DosR regulon proteins. Aerated cultures showed higher levels of proteins involved in transcription, translation, DNA replication, and virulence. Protein secretion decreased under hypoxia. Overall, <em>M. bovis</em> remodels its proteome to persist in a viable, non-replicative state.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102739"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038656","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":"Single-cell transcriptomics reveals phenotypic and functional alterations of erythroid progenitor cells in tuberculosis patients","authors":"Hao Zhang ,&nbsp;Yan Cao ,&nbsp;Ling Yang ,&nbsp;Bowen Liu ,&nbsp;Jingzhi Guan ,&nbsp;Xinjing Wang","doi":"10.1016/j.tube.2026.102746","DOIUrl":"10.1016/j.tube.2026.102746","url":null,"abstract":"<div><div>Anemia is a common complication of tuberculosis (TB), closely associated with impaired host immune function and poor prognosis; however, its impact on the dynamic alterations of erythroid progenitor cells (EPCs) remains largely unexplored. In this study, we integrated and analyzed single-cell transcriptomic data from peripheral blood mononuclear cells (PBMC) of healthy controls, latent tuberculosis (LTB), TB, and disseminated tuberculosis (DTB) cohorts, as well as 18F-FDG-labeled TB lung tissues and adjacent uninvolved regions. At single-cell resolution, we identified ten EPCs clusters within PBMC, among which clusters 2–6 represented DTB-specific subpopulations (EPC_DTB). These EPC_DTB exhibited metabolic reprogramming (including glycolysis, arginine, and lipid metabolism) accompanied by upregulation of IFITM3/JUN and ribosomal genes, consistent with enhanced differentiation. EPC_DTB and EPC_TB interacted with macrophages, dendritic cells, and monocytes through the ANNEXIN and GALECTIN signaling pathways, while these immune cells reciprocally regulated EPCs subsets via the MIF signaling axis. In lung tissues, EPCs (12 clusters) displayed disease-specific characteristics, with clusters 0, 3, and 6 uniquely present in TB lesions. The EPC_High subpopulation within inflammatory foci showed significant upregulation of GZMA, IL32, CCL5, and CHI3L1, whereas EPC_Low communicated with immune cells, epithelial cells, and stromal cells through the MDK–NCL signaling pathway. Moreover, we established an LTB predictive model based on EPC_LTB signature genes in PBMC (GRIK3, S100B, ZDHHC19, and LRRN3). Our study uncovers the heterogeneity of EPCs across different TB stages and tissue compartments, delineates their bidirectional crosstalk with immune cells, and establishes a link among anemia, immune regulation, and EPCs biology, thereby proposing potential diagnostic biomarkers and therapeutic targets.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102746"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285168","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":"Migrations and Tuberculosis: A comparative study of Mycobacterium tuberculosis genomic population structure in Brazil and Mozambique to historical triangular slave trade knowledge to reconstruct the origins of tuberculosis infections caused by Lineage 1 in Brazil","authors":"Thibaut Morel-Journel ,&nbsp;Christophe Guyeux ,&nbsp;Christophe Sola","doi":"10.1016/j.tube.2026.102734","DOIUrl":"10.1016/j.tube.2026.102734","url":null,"abstract":"<div><div>Lineage 1 is an ancestral lineage of the <em>Mycobacterium tuberculosis</em> complex (MTBC) comprising five sublineages. In a previous study, we suggested that a representative of sublineage L1.1.3, present in both Mozambique and northern Brazil, SIT129, may have been brought to Brazil by sea during the long history of slavery that lasted, between Africa and Brazil, from the early 16th century to the mid-19th century. In this study, using a combination of new comparative genomics results and human migration data extracted from the <span><span>SlaveVoyages.org</span><svg><path></path></svg></span> database, we sought to more precisely reconstruct the scenario for the introduction of L1 genotypes into Brazil. We present results showing substantial similarities between the MTBC population structure in present-day Mozambique and Brazil across three subclades, L1.1.2, L1.1.3, and L1.2.2, and convergent historical data. Indeed, several introductions between the 16th and 19th centuries could explain the higher contemporary prevalence of L1 in northern Brazil. Our data do not allow us to decide between a direct introduction of L1 isolates into northern Brazil and intra-Brazilian transmission from the main southern ports, which seems likely. Other less likely scenarios are also discussed.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102734"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915297","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":"Diagnostic evaluation of a novel recombinant multi-epitope protein for paucibacillary and multibacillary leprosy","authors":"César N. Pereira ,&nbsp;Raquel S.B. Câmara ,&nbsp;Daniela P. Lage ,&nbsp;Laís V.A. Corrêa ,&nbsp;Camila S. Freitas ,&nbsp;Ana L. Silva ,&nbsp;Nathália C. Galvani ,&nbsp;Mariana M. Cardoso ,&nbsp;Bárbara P.N. Assis ,&nbsp;Miguel A. Chávez-Fumagalli ,&nbsp;Ricardo A. Machado-de-Ávila ,&nbsp;Alexsandro S. Galdino ,&nbsp;Unaí Tupinambás ,&nbsp;Lílian L. Bueno ,&nbsp;Ricardo T. Fujiwara ,&nbsp;Manoel O. da Costa Rocha ,&nbsp;Denise U. Gonçalves ,&nbsp;Myron Christodoulides ,&nbsp;Ana T. Chaves ,&nbsp;Eduardo A.F. Coelho ,&nbsp;Isabela A.G. Pereira","doi":"10.1016/j.tube.2026.102732","DOIUrl":"10.1016/j.tube.2026.102732","url":null,"abstract":"<div><div>The diagnosis of leprosy remains challenging due to its clinical similarity with other infectious diseases and the variable sensitivity and specificity of current laboratory tests. Therefore, the identification and/or development of novel antigens is crucial for improving diagnostic accuracy. In this study, we designed a novel recombinant multi-polypeptide construct, termed M3, which was composed of specific B-cell epitopes from nine <em>Mycobacterium leprae</em> proteins, previously shown to be antigenic in leprosy. The recombinant M3 protein was expressed, purified, and evaluated as an antigen for the diagnosis of both paucibacillary (PB) and multibacillary (MB) disease, by using paired serum and urine samples from 380 participants. ELISA was performed using samples from PB (n = 50) and MB (n = 55) leprosy patients, their household contacts [PBC (n = 30) and MBC (n = 40), respectively], healthy individuals living in endemic region (n = 55), and patients with visceral (n = 30) and tegumentary (n = 45) leishmaniasis, Chagas disease (n = 35), tuberculosis (n = 15), and HIV-infection (n = 25). In serum-based ELISA, M3 showed sensitivity, specificity, positive and negative predictive values, and Youden index of 94.5 %, 100 %, 96.8 %, 97.4 %, and 0.91, respectively; whilst in a urine-based ELISA, the corresponding values were 96.4 %, 100 %, 98.8 %, 98.2 %, and 0.96, respectively. Additionally, paired serum and urine samples from 15 PB and 20 MB patients collected before and after treatment, revealed that anti-M3 antibodies decreased by more than 50 % post-therapy when using both analytes. These pilot findings suggest a potential biological role of the recombinant M3 protein for diagnosis of PB and MB leprosy.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102732"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915296","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":"Comment on “Dysregulated IFN-γ, IL-6 and TNF α after COVID-19 is suggestive of lowered innate immune responses to SARS-CoV-2 and MTB”","authors":"Prashant Ramdas Kokiwar,&nbsp;Ambreen Singh Chauhan,&nbsp;A. Kavya,&nbsp;Archana Dhyani","doi":"10.1016/j.tube.2026.102737","DOIUrl":"10.1016/j.tube.2026.102737","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102737"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985615","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":"Response to comments for: Dysregulated IFN-γ, IL-6 and TNF-α after COVID-19 is suggestive of lowered innate immune responses to SARS-CoV-2 and MTB","authors":"Uzair Abbas ,&nbsp;Kiran Iqbal Masood ,&nbsp;Tulaib Iqbal ,&nbsp;Shama Qaiser ,&nbsp;Martin Rottenberg ,&nbsp;Bushra Jamil ,&nbsp;Rabia Hussain ,&nbsp;Zahra Hasan","doi":"10.1016/j.tube.2026.102738","DOIUrl":"10.1016/j.tube.2026.102738","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102738"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998886","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 role of programmed cell death pathways in the host response to Mycobacterium tuberculosis: Insights from gene expression analysis in active pulmonary tuberculosis patients","authors":"Qifeng Li ,&nbsp;Maierheba Kuerbanjiang ,&nbsp;Jianfeng Zhang ,&nbsp;Dan Chen ,&nbsp;Gaofeng Sun ,&nbsp;Zhigang Liu","doi":"10.1016/j.tube.2026.102741","DOIUrl":"10.1016/j.tube.2026.102741","url":null,"abstract":"<div><div>Tuberculosis, primarily caused by <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>), remains a leading global health issue. We investigate the interplay between <em>Mtb</em> infection and various programmed cell death (PCD) in active pulmonary tuberculosis (ATB). Using GSE19491 and GSE107994 datasets, we identified 1306 overlapping differentially expressed genes (DEGs) in peripheral blood from ATB patients and healthy controls. Gene set variation analysis revealed that, except for cuproptosis, the PCD pathways: necroptosis, apoptosis, pyroptosis, and ferroptosis were significantly elevated in ATB patients. Weighted Gene Co-expression Network Analysis further identified 392 PCD-associated hub genes. KEGG and GO analyses highlighted key functional enrichments in immune responses, cellular stress, and PCD pathways. Moreover, we found a positive correlation between PCD types and specific immune cell populations. Additionally, by integrating DEGs of peripheral blood samples and lung granuloma tissues with PCD-associated hub genes, we identified 30 PCD-related genes in ATB patients. RT-qPCR results demonstrated significantly elevated GCLC, RBCK1, ZEB1, and EIF2AK2 levels, alongside lowered PLA2G4C and CAMK2G levels in patients’ peripheral blood. These findings underscore the critical role of PCD pathways in modulating the immune response during <em>Mtb</em> infection. Future mechanistic studies are required to definitively establish the causal roles of these pathways in regulating cell death and bacterial control.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102741"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107359","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}