Frontiers in Cellular and Infection Microbiology最新文献

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Cellular SUMO-specific proteases regulate HAdV-C5 E1B-55K SUMOylation and virus-induced cell transformation. 细胞SUMO特异性蛋白酶调控HAdV-C5 E1B-55K SUMOylation和病毒诱导的细胞转化。
IF 4.6 2区 医学
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-27 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1484241
Wing-Hang Ip, Marie Fiedler, Britta Gornott, Malte Morische, Luca D Bertzbach, Thomas Dobner
{"title":"Cellular SUMO-specific proteases regulate HAdV-C5 E1B-55K SUMOylation and virus-induced cell transformation.","authors":"Wing-Hang Ip, Marie Fiedler, Britta Gornott, Malte Morische, Luca D Bertzbach, Thomas Dobner","doi":"10.3389/fcimb.2024.1484241","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1484241","url":null,"abstract":"<p><p>Various viral proteins are post-translationally modified by SUMO-conjugation during the human adenovirus (HAdV) replication cycle. This modification leads to diverse consequences for target proteins as it influences their intracellular localization or cell transformation capabilities. SUMOylated HAdV proteins include the multifunctional oncoprotein E1B-55K. Our previous research, along with that of others, has demonstrated a substantial influence of yet another adenoviral oncoprotein, E4orf6, on E1B-55K SUMOylation levels. Protein SUMOylation can be reversed by cellular sentrin/SUMO-specific proteases (SENPs). In this study, we investigated the interaction of E1B-55K with cellular SENPs to understand deSUMOylation activities and their consequences for cell transformation mediated by this adenoviral oncoprotein. We show that E1B-55K interacts with and is deSUMOylated by SENP 1, independently of E4orf6. Consistent with these results, we found that SENP 1 prevents E1A/E1B-dependent focus formation in rodent cells. We anticipate these findings to be the groundwork for future studies on adenovirus-host interactions, the mechanisms that underlie E1B-55K SUMOylation, as well as the role of this major adenoviral oncoprotein in HAdV-mediated cell transformation.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The gut microbiota: emerging biomarkers and potential treatments for infertility-related diseases. 肠道微生物群:不孕症相关疾病的新兴生物标志物和潜在治疗方法。
IF 4.6 2区 医学
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-26 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1450310
Min Wang, Lian-Wen Zheng, Shuai Ma, Dong-Hai Zhao, Ying Xu
{"title":"The gut microbiota: emerging biomarkers and potential treatments for infertility-related diseases.","authors":"Min Wang, Lian-Wen Zheng, Shuai Ma, Dong-Hai Zhao, Ying Xu","doi":"10.3389/fcimb.2024.1450310","DOIUrl":"10.3389/fcimb.2024.1450310","url":null,"abstract":"<p><p>Infertility is a disease of impaired fertility. With socioeconomic development, changes in human lifestyles, and increased environmental pollution, the problem of low human fertility has become increasingly prominent. The incidence of global infertility is increasing every year. Many factors lead to infertility, and common female factors include tubal factors, ovulation disorders, endometriosis, and immune factors. The gut microbiota is involved in many physiological processes, such as nutrient absorption, intestinal mucosal growth, glycolipid metabolism, and immune system regulation. An altered gut flora is associated with female infertility disorders such as polycystic ovary syndrome (PCOS), endometriosis (EMs), and premature ovarian failure (POF). Dysbiosis of the gut microbiota directly or indirectly contributes to the development of female infertility disorders, which also affect the homeostasis of the gut microbiota. Identifying the etiology and pathogenesis of infertility in patients is the focus of reproductive medicine physicians. We studied the developmental mechanism between the gut microbiota and PCOS, EMs, and POF from a new perspective, providing new ideas for diagnosing and treating female infertility diseases and specific reference values for eugenics.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical and genomic characterization of carbapenem-resistant Enterobacterales bloodstream infections in patients with hematologic malignancies. 血液系统恶性肿瘤患者耐碳青霉烯类肠杆菌血流感染的临床和基因组特征。
IF 4.6 2区 医学
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-26 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1471477
Yi Chen, Jiangqing Huang, Luyan Dong, Binbin Xu, Lei Li, Zhichang Zhao, Bin Li
{"title":"Clinical and genomic characterization of carbapenem-resistant <i>Enterobacterales</i> bloodstream infections in patients with hematologic malignancies.","authors":"Yi Chen, Jiangqing Huang, Luyan Dong, Binbin Xu, Lei Li, Zhichang Zhao, Bin Li","doi":"10.3389/fcimb.2024.1471477","DOIUrl":"10.3389/fcimb.2024.1471477","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant <i>Enterobacterales</i> (CRE) bloodstream infections (BSIs) pose a significant risk to patients with hematologic malignancies, yet the distinct features and outcomes of these infections are not thoroughly understood.</p><p><strong>Methods: </strong>This retrospective study examined the characteristics and clinical outcomes of patients with <i>Enterobacterales</i> BSIs at the Hematology Department of Fujian Medical University Union Hospital from 2018 to 2022. Whole-genome sequencing was conducted on 45 consecutive CRE BSI isolates during this period.</p><p><strong>Results: </strong>A total of 301 patients with <i>Enterobacterales</i> BSIs were included, with 65 (21.6%) cases of CRE and 236 (78.4%) cases of carbapenem-susceptible <i>Enterobacterales</i> (CSE). CRE infections accounted for 16.9% to 26.9% of all <i>Enterobacterales</i> BSIs, and carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) was the predominant strain. The most frequent sequence type (ST) and carbapenemase among CRKP were ST11 (68.6%) and <i>bla</i>KPC-2 (80.0%), respectively. Perianal infections, multiple infection foci, and a history of multiple hospitalizations, ICU stays, and prior CRE infections were identified as risk factors for CRE BSIs. Patients in the CRE group experienced significantly higher proportions of infection-related septic shock (43.1% vs. 19.9%, P < 0.0003) and 30-day all-cause mortality (56.9% vs. 24.6%, P < 0.0001) compared to those in the CSE group. Patient's age and disease subtypes, strain subtypes, and antimicrobial treatment regimens significantly influenced survival in patients with CRE BSIs.</p><p><strong>Conclusions: </strong>CRE BSIs are a frequent complication in patients with hematological malignancies undergoing treatment and are associated with poor survival rates. A comprehensive understanding of risk factors and ongoing surveillance of prevalent strains are essential for the effective management of these infections.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Approved drugs successfully repurposed against Leishmania based on machine learning predictions. 根据机器学习预测,成功将已批准的药物重新用于防治利什曼病。
IF 4.6 2区 医学
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-26 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1403589
Rafeh Oualha, Yosser Zina Abdelkrim, Ikram Guizani, Emna Harigua-Souiai
{"title":"Approved drugs successfully repurposed against <i>Leishmania</i> based on machine learning predictions.","authors":"Rafeh Oualha, Yosser Zina Abdelkrim, Ikram Guizani, Emna Harigua-Souiai","doi":"10.3389/fcimb.2024.1403589","DOIUrl":"10.3389/fcimb.2024.1403589","url":null,"abstract":"<p><p>Drug repurposing is a promising approach towards the discovery of novel treatments against Neglected Tropical Diseases, such as Leishmaniases, presenting the advantage of reducing both costs and duration of the drug discovery process. In previous work, our group developed a Machine Learning pipeline for the repurposing of FDA-approved drugs against <i>Leishmania</i> parasites. The present study is focused on an <i>in vitro</i> validation of this approach by assessing the antileishmanial effects of 10 predicted drug candidates. First, we evaluated the drugs' activity against promastigotes from two strains of <i>L. infantum</i> and one of <i>L. major</i>, which caused distinct clinical manifestations, using an MTT assay. The standard anti-<i>Leishmania</i> drug Amphotericin B was used as a positive control. Five molecules demonstrated anti-<i>Leishmania</i> effects, out of which Acebutolol, Prilocaine and Phenylephrine are described herein for the first time. When tested on promastigote growth, Acebutolol displayed IC<sub>50</sub> values ranging from 69.28 to 145.53 µg/mL. Prilocaine exhibited IC<sub>50</sub> values between 33.10 and 45.81 µg/mL. Phenylephrine, on the other hand, presented IC<sub>50</sub> values >200 µg/mL. The two remaining drugs, Dibucaine and Domperidone, exhibited significantly low IC<sub>50</sub> values varying between 0.58 and 1.05 µg/mL, and 6.30 and 8.17 µg/mL, respectively. Both compounds were previously described as anti-<i>Leishmania</i> agents <i>in vivo</i>. All five compounds demonstrated no notable cytotoxic effects on THP-1-derived macrophages at the IC<sub>50</sub> concentrations, allowing for their testing on the intracellular form of <i>L. major</i> and <i>L. infantum</i> parasites. Interestingly, all compounds exhibited antileishmanial activity on amastigotes with enhanced IC<sub>50</sub> values compared to the corresponding promastigotes. Noticeably, Dibucaine and Domperidone displayed IC<sub>50</sub> values of at most 1.99 µg/mL. Acebutolol, Prilocaine and Phenylephrine showed IC<sub>50</sub> values ranging from 13.84 to 66.81 µg/mL. Our previously published Computer-Aided repositioning pipelines of FDA-approved drugs as antileishmanial agents identified Dibucaine and Domperidone as candidates in support of previous <i>in vivo</i> studies. This study consolidates such findings through the <i>in vitro</i> validation against 2 <i>Leishmania</i> species, highly prevalent in Africa and Middle East, and reveals Acebutolol, Prilocaine, and Phenylephrine as novel anti-<i>Leishmania</i> effectors, confirming the relevance of our approach and calling for further investigations.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Progress in the study of the correlation between sepsis and intestinal microecology. 败血症与肠道微生态学相关性研究的进展。
IF 4.6 2区 医学
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-26 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1357178
Yan-Lin Tao, Jing-Ran Wang, Miao Liu, Ya-Nan Liu, Jin-Qiu Zhang, Yi-Jing Zhou, Shao-Wei Li, Shu-Fen Zhu
{"title":"Progress in the study of the correlation between sepsis and intestinal microecology.","authors":"Yan-Lin Tao, Jing-Ran Wang, Miao Liu, Ya-Nan Liu, Jin-Qiu Zhang, Yi-Jing Zhou, Shao-Wei Li, Shu-Fen Zhu","doi":"10.3389/fcimb.2024.1357178","DOIUrl":"10.3389/fcimb.2024.1357178","url":null,"abstract":"<p><p>Sepsis, a disease with high incidence, mortality, and treatment costs, has a complex interaction with the gut microbiota. With advances in high-throughput sequencing technology, the relationship between sepsis and intestinal dysbiosis has become a new research focus. However, owing to the intricate interplay between critical illness and clinical interventions, it is challenging to establish a causal relationship between sepsis and intestinal microbiota imbalance. In this review, the correlation between intestinal microecology and sepsis was summarized, and new therapies for sepsis intervention based on microecological target therapy were proposed, and the shortcomings of bacterial selection and application timing in clinical practice were addressed. In conclusion, current studies on metabolomics, genomics and other aspects aimed at continuously discovering potential probiotics are all providing theoretical basis for restoring intestinal flora homeostasis for subsequent treatment of sepsis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum: Antibiotic resistance: One Health One World outlook. 更正:抗生素耐药性:一个健康一个世界 "展望。
IF 4.6 2区 医学
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-25 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1488430
Bilal Aslam, Mohsin Khurshid, Muhammad Imran Arshad, Saima Muzammil, Maria Rasool, Nafeesa Yasmeen, Taif Shah, Tamoor Hamid Chaudhry, Muhammad Hidayat Rasool, Aqsa Shahid, Xia Xueshan, Zulqarnain Baloch
{"title":"Corrigendum: Antibiotic resistance: One Health One World outlook.","authors":"Bilal Aslam, Mohsin Khurshid, Muhammad Imran Arshad, Saima Muzammil, Maria Rasool, Nafeesa Yasmeen, Taif Shah, Tamoor Hamid Chaudhry, Muhammad Hidayat Rasool, Aqsa Shahid, Xia Xueshan, Zulqarnain Baloch","doi":"10.3389/fcimb.2024.1488430","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1488430","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fcimb.2021.771510.].</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From gut to bone: deciphering the impact of gut microbiota on osteoporosis pathogenesis and management. 从肠道到骨骼:解读肠道微生物群对骨质疏松症发病机制和管理的影响。
IF 4.6 2区 医学
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-25 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1416739
Linjie Hao, Yuzhu Yan, Guilin Huang, Hui Li
{"title":"From gut to bone: deciphering the impact of gut microbiota on osteoporosis pathogenesis and management.","authors":"Linjie Hao, Yuzhu Yan, Guilin Huang, Hui Li","doi":"10.3389/fcimb.2024.1416739","DOIUrl":"10.3389/fcimb.2024.1416739","url":null,"abstract":"<p><p>Osteoporosis (OP) is characterized by decreased bone mineral density (BMD) and increased fracture risk, poses a significant global health burden. Recent research has shed light on the bidirectional relationship between gut microbiota (GM) and bone health, presenting a novel avenue for understanding OP pathogenesis and developing targeted therapeutic interventions. This review provides a comprehensive overview of the GM-bone axis, exploring the impact of GM on OP development and management. We elucidate established risk factors and pathogenesis of OP, delve into the diversity and functional changes of GM in OP. Furthermore, we examine experimental evidence and clinical observations linking alterations in GM composition or function with variations in BMD and fracture risk. Mechanistic insights into microbial mediators of bone health, such as microbial metabolites and products, are discussed. Therapeutic implications, including GM-targeted interventions and dietary strategies, are also explored. Finally, we identify future research directions and challenges in translating these findings into clinical practice.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aptamers: precision tools for diagnosing and treating infectious diseases. 肽聚体:诊断和治疗传染病的精确工具。
IF 4.6 2区 医学
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-25 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1402932
Swathi Sujith, Rajalakshmi Naresh, B U Srivisanth, Anusree Sajeevan, Shobana Rajaramon, Helma David, Adline Princy Solomon
{"title":"Aptamers: precision tools for diagnosing and treating infectious diseases.","authors":"Swathi Sujith, Rajalakshmi Naresh, B U Srivisanth, Anusree Sajeevan, Shobana Rajaramon, Helma David, Adline Princy Solomon","doi":"10.3389/fcimb.2024.1402932","DOIUrl":"10.3389/fcimb.2024.1402932","url":null,"abstract":"<p><p>Infectious diseases represent a significant global health challenge, with bacteria, fungi, viruses, and parasitic protozoa being significant causative agents. The shared symptoms among diseases and the emergence of new pathogen variations make diagnosis and treatment complex. Conventional diagnostic methods are laborious and intricate, underscoring the need for rapid, accurate techniques. Aptamer-based technologies offer a promising solution, as they are cost-effective, sensitive, specific, and convenient for molecular disease diagnosis. Aptamers, which are single-stranded RNA or DNA sequences, serve as nucleotide equivalents of monoclonal antibodies, displaying high specificity and affinity for target molecules. They are structurally robust, allowing for long-term storage without substantial activity loss. Aptamers find applications in diverse fields such as drug screening, material science, and environmental monitoring. In biomedicine, they are extensively studied for biomarker detection, diagnostics, imaging, and targeted therapy. This comprehensive review focuses on the utility of aptamers in managing infectious diseases, particularly in the realms of diagnostics and therapeutics.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Distinct characteristics of BTLA/HVEM axis expression on Tregs and its impact on the expansion and attributes of Tregs in patients with active pulmonary tuberculosis. 活动性肺结核患者 Tregs 上 BTLA/HVEM 轴表达的不同特征及其对 Tregs 扩增和属性的影响。
IF 4.6 2区 医学
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-25 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1437207
Peijun Tang, Xinghua Shen, Jianling Gao, Jianping Zhang, Yanjun Feng, Ji Zhang, Ziyi Huang, Xuefeng Wang
{"title":"Distinct characteristics of BTLA/HVEM axis expression on Tregs and its impact on the expansion and attributes of Tregs in patients with active pulmonary tuberculosis.","authors":"Peijun Tang, Xinghua Shen, Jianling Gao, Jianping Zhang, Yanjun Feng, Ji Zhang, Ziyi Huang, Xuefeng Wang","doi":"10.3389/fcimb.2024.1437207","DOIUrl":"10.3389/fcimb.2024.1437207","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary tuberculosis (PTB) remains one of the deadliest infectious diseases. Understanding PTB immunity is of potential value for exploring immunotherapy for treating chemotherapy-resistant PTB. CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells (Tregs) are key players that impair immune responses to <i>Mycobacteria tuberculosis</i> (MTB). Currently, the intrinsic factors governing Treg expansion and influencing the immunosuppressive attributes of Tregs in PTB patients are far from clear.</p><p><strong>Methods: </strong>Here, we employed flow cytometry to determine the frequency of Tregs and the expression of B and T lymphocyte attenuator (BTLA) and its ligand, herpesvirus entry mediator (HVEM), on Tregs in patients with active PTB. Furthermore, the expression of conventional T cells and of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) on Tregs in patients with active PTB was determined. We then examined the characteristics of BTLA/HVEM expression and its correlation with Treg frequency and PD-L1 and PD-1 expression on Tregs in PTB patients.</p><p><strong>Results: </strong>The frequency of Tregs was increased in PTB patients and it had a relevance to PTB progression. Intriguingly, the axis of cosignal molecules, BTLA and HVEM, were both downregulated on the Tregs of PTB patients compared with healthy controls (HCs), which was the opposite of their upregulation on conventional T cells. Unexpectedly, their expression levels were positively correlated with the frequency of Tregs, respectively. These seemingly contradictory results may be interpreted as follows: the downregulation of BTLA and HVEM may alleviate BTLA/HVEM <i>cis</i>-interaction-mediated coinhibitory signals pressing on naïve Tregs, helping their activation, while the BTLA/HVEM axis on effector Tregs induces a costimulatory signal, promoting their expansion. Certainly, the mechanism underlying such complex effects remains to be explored. Additionally, PD-L1 and PD-1, regarded as two of the markers characterizing the immunosuppressive attributes and differentiation potential of Tregs, were upregulated on the Tregs of PTB patients. Further analysis revealed that the expression levels of BTLA and HVEM were positively correlated with the frequency of PD-1<sup>+</sup>Tregs and PD-L1<sup>+</sup>Tregs, respectively.</p><p><strong>Conclusion: </strong>Our study illuminated distinct characteristics of BTLA/HVEM axis expression on Tregs and uncovered its impact on the expansion and attributes of Tregs in patients with active PTB. Therefore, blockade of the BTLA/HVEM axis may be a promising potential pathway to reduce Treg expansion for the improvement of anti-MTB immune responses.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive insights into UTIs: from pathophysiology to precision diagnosis and management. 全面了解尿毒症:从病理生理学到精确诊断和管理。
IF 4.6 2区 医学
Frontiers in Cellular and Infection Microbiology Pub Date : 2024-09-24 eCollection Date: 2024-01-01 DOI: 10.3389/fcimb.2024.1402941
Swathi Sujith, Adline Princy Solomon, John Bosco Balaguru Rayappan
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