Journal of Extracellular Vesicles最新文献_第3页

Plasma Extracellular Vesicle-Derived miR-296-5p is a Maturation-Dependent Rejuvenation Factor that Downregulates Inflammation and Improves Survival after Sepsis 血浆细胞外囊泡来源的miR-296-5p是一种成熟依赖的恢复因子，可下调炎症并提高脓毒症后的生存率

IF 15.5 1区医学

Journal of Extracellular Vesicles Pub Date : 2025-04-26 DOI: 10.1002/jev2.70065

Lun Cai, Parmita Kar, Yutao Liu, Xiaogang Chu, Ashok Sharma, Tae Jin Lee, Ali Arbab, Raghavan Pillai Raju

{"title":"Plasma Extracellular Vesicle-Derived miR-296-5p is a Maturation-Dependent Rejuvenation Factor that Downregulates Inflammation and Improves Survival after Sepsis","authors":"Lun Cai, Parmita Kar, Yutao Liu, Xiaogang Chu, Ashok Sharma, Tae Jin Lee, Ali Arbab, Raghavan Pillai Raju","doi":"10.1002/jev2.70065","DOIUrl":"https://doi.org/10.1002/jev2.70065","url":null,"abstract":"There is a progressive decline in physiological function with age, and aging is associated with increased susceptibility to injury and infection. However, several reports have indicated that the agility of youth is characterized by transferable rejuvenating molecular factors, as was observed previously in heterochronic parabiosis experiments. These experiments demonstrated a rejuvenating effect of young blood in old animals. There have been several efforts to characterize these youthful or maturation-associated factors in the young blood. In this report, we demonstrate the resilience of young mice, at or before puberty, to polymicrobial sepsis and show an age-dependent effect of small extracellular vesicles (EVs) from plasma on the outcome following sepsis. The EVs from the young mice were cytoprotective, anti-inflammatory, and reduced cellular senescence markers. MicroRNA sequencing of the EVs showed an age-associated signature and identified miR-296-5p and miR-541-5p to progressively reduce their levels in the blood plasma with increasing age. We further show that the levels of these miRNAs decline with age in multiple organs. The miRNAs miR-296-5p and miR-541-5p showed a reparatory effect in an in vitro wound healing model and the miR-296-5p, when given intraperitoneally, reduced mortality in the mouse model of sepsis. In summary, our studies demonstrate that EVs from very young mice have a reparative effect on sepsis, and the reparative factors are likely maturation-dependent. Our observation that miR-296-5p and miR-541-5p are plasma EV constituents that significantly reduce with age and can reduce inflammation suggests a therapeutic potential for these miRNAs in inflammation and age-associated diseases.","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Correction to "DetectEV: a Functional Enzymatic Assay to Assess Integrity and Bioactivity of Extracellular Vesicles" DetectEV: 评估细胞外囊泡完整性和生物活性的功能酶测定 "的更正

IF 15.5 1区医学

Journal of Extracellular Vesicles Pub Date : 2025-04-16 DOI: 10.1002/jev2.70075

引用次数: 0

Small Extracellular Vesicle-Derived Nicotinamide Phosphoribosyltransferase (NAMPT) Induces Acyl-Coenzyme A Synthetase SLC27A4-Mediated Glycolysis to Promote Hepatocellular Carcinoma 细胞外小泡衍生的烟酰胺磷酸核糖基转移酶（NAMPT）诱导酰基辅酶A合成酶slc27a4介导的糖酵解促进肝细胞癌

IF 15.5 1区医学

Journal of Extracellular Vesicles Pub Date : 2025-04-16 DOI: 10.1002/jev2.70071

Cherlie Lot Sum Yeung, Tung Him Ng, Charlotte Jiaqi Lai, Tingmao Xue, Xiaowen Mao, Sze Keong Tey, Regina Cheuk Lam Lo, Chun-Fung Sin, Kwan Ming Ng, Danny Ka Ho Wong, Lung-Yi Mak, Man-Fung Yuen, Irene Oi-Lin Ng, Peihua Cao, Yi Gao, Jing Ping Yun, Judy Wai Ping Yam

{"title":"Small Extracellular Vesicle-Derived Nicotinamide Phosphoribosyltransferase (NAMPT) Induces Acyl-Coenzyme A Synthetase SLC27A4-Mediated Glycolysis to Promote Hepatocellular Carcinoma","authors":"Cherlie Lot Sum Yeung, Tung Him Ng, Charlotte Jiaqi Lai, Tingmao Xue, Xiaowen Mao, Sze Keong Tey, Regina Cheuk Lam Lo, Chun-Fung Sin, Kwan Ming Ng, Danny Ka Ho Wong, Lung-Yi Mak, Man-Fung Yuen, Irene Oi-Lin Ng, Peihua Cao, Yi Gao, Jing Ping Yun, Judy Wai Ping Yam","doi":"10.1002/jev2.70071","DOIUrl":"https://doi.org/10.1002/jev2.70071","url":null,"abstract":"Tumour-derived small extracellular vesicles (sEV) are critical mediators within the tumour microenvironment (TME) and are known to regulate various metabolic pathways. In metastatic hepatocellular carcinoma (HCC), mass spectrometry protein analysis of HCC-derived sEV (HCC-sEV) identified an upregulation of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in maintaining cellular nicotinamide adenine dinucleotide (NAD+) levels. Our study demonstrates that sEV-NAMPT enhances glycolysis, tumorigenesis, and metastasis in HCC. Specifically, sEV-NAMPT activates the NF-κB transcription factor through toll-like receptor 4 (TLR4), leading to elevated SLC27A4 expression. SLC27A4 functions primarily as a long-chain fatty acid transporter and acyl-CoA synthetase. Lipidomic and metabolomic analyses revealed a positive correlation between SLC27A4 and intracellular levels of triacylglycerol (TG) and dihydroxyacetone phosphate (DHAP). Increased TG levels enhance lipolysis via hepatic lipase and facilitate the conversion of glycerol-3-P to DHAP, an intermediate that bridges lipid metabolism and glycolysis. This study uncovers a novel regulatory axis involving sEV-NAMPT and SLC27A4 in glycolysis, independent of traditional fatty acid metabolism pathways. Clinically, targeting sEV-NAMPT with the inhibitor FK866 significantly inhibited tumour growth in various HCC in vivo models, highlighting the potential of sEV-NAMPT as both a biomarker and therapeutic target in HCC.","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Microbead Encapsulation Strategy for Efficient Production of Extracellular Vesicles Derived From Human Mesenchymal Stem Cells 高效生产人间质干细胞胞外囊泡的微珠封装策略

IF 15.5 1区医学

Journal of Extracellular Vesicles Pub Date : 2025-04-16 DOI: 10.1002/jev2.70053

Yunxia Hu, Lijuan Zheng, Zheng Zheng, Mali Fu, Haiying Peng, Shaohua Ma

{"title":"Microbead Encapsulation Strategy for Efficient Production of Extracellular Vesicles Derived From Human Mesenchymal Stem Cells","authors":"Yunxia Hu, Lijuan Zheng, Zheng Zheng, Mali Fu, Haiying Peng, Shaohua Ma","doi":"10.1002/jev2.70053","DOIUrl":"https://doi.org/10.1002/jev2.70053","url":null,"abstract":"Human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) have shown great potential in tissue repair and regeneration. However, their scalable production and functional quality are still limited by current expansion technologies. In this study, we propose a production technology for hMSC-EVs based on three-dimensional (3D) microbead culture, which enhances the secretory behaviour of hMSC. Fixed number of MSCs were encapsulated in Matrigel at appropriate densities and printed into 3D microbeads by the custom automated microfluidic bead-jet printing technique. Compared with 2D culture group, EVs derived from 3D hMSC microbead had smaller size and increased yield by 20-fold, and the actin depolymerisation of the cell may be an important mechanism for enhancing EV secretion. Further analysis confirmed that the EVs derived from 3D hMSC microbead exhibited enhanced angiogenic and proliferative capabilities, which promoted the viability and tube-forming capacity of human umbilical vein endothelial cells (HUVEC). In conclusion, this automated microfluidic microbead encapsulation technology increased the yield and therapeutic effect of hMSC-EVs and provides a platform for scalable EV production of regenerative therapies.","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Dendritic Cell Derived-Extracellular Vesicles Engineered to Express Interleukin-12 and Anti-CTLA-4 on Their Surface for Combinational Cancer Immunotherapy 树突状细胞衍生的细胞外囊泡在其表面表达白细胞介素-12和抗ctla -4用于联合癌症免疫治疗

IF 15.5 1区医学

Journal of Extracellular Vesicles Pub Date : 2025-04-16 DOI: 10.1002/jev2.70068

Jiangbin Chen, Qi Tan, Zimo Yang, Wenjuan Chen, E. Zhou, Minglei Li, Jingjing Deng, Yali Wu, Jiatong Liu, Juanjuan Xu, Mengfei Guo, Yang Jin

{"title":"Dendritic Cell Derived-Extracellular Vesicles Engineered to Express Interleukin-12 and Anti-CTLA-4 on Their Surface for Combinational Cancer Immunotherapy","authors":"Jiangbin Chen, Qi Tan, Zimo Yang, Wenjuan Chen, E. Zhou, Minglei Li, Jingjing Deng, Yali Wu, Jiatong Liu, Juanjuan Xu, Mengfei Guo, Yang Jin","doi":"10.1002/jev2.70068","DOIUrl":"https://doi.org/10.1002/jev2.70068","url":null,"abstract":"Dendritic cell (DC)-derived extracellular vesicles (DEVs) are promising candidates for cancer vaccines, but their therapeutic effects still need further optimization. In this study, we utilized neoantigens, lipopolysaccharide and IFN-γ to induce the maturation of DCs, and then isolated DEVs derived from these mature DCs. We showed that the immune checkpoint inhibitor (anti-CTLA-4 antibody, aCTLA-4) can improve the immunostimulatory function of DEVs by directly activating T cells through immune checkpoint signal blockade. The cytokine interleukin-12 (IL-12), as one of the third signals for T cell activation, can also enhance the capability of DEVs to activate T cells directly. Based on these findings, we designed the engineered DEVs conjugated with IL-12 and aCTLA-4 (DEV@IL-12-aCTLA-4) to improve the therapeutic potential of DEVs by providing sufficient immune regulatory signals. Moreover, the carrier property of DEVs also contributes to the delivery of IL-12 and aCTLA-4 to lymph nodes. This indicates that the conjugation of DEVs with IL-12 and aCTLA-4 constitutes a complementary approach, where IL-12 and aCTLA-4 help to enhance the T cell activation effect of DEVs, and DEVs facilitate the delivery of IL-12 and aCTLA-4. Our results showed that DEV@IL-12-aCTLA-4 can enhance the Th1 immune response and reverse exhausted CD8+ T cells in the tumour microenvironment, effectively inducing robust T cell immune responses and inhibiting tumour growth in tumour-bearing mice. Overall, this study expands the theoretical foundation of DEVs and provides a universal strategy for optimizing cancer combination immunotherapy by reprogramming DEVs.","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Nanobody Engineered and Photosensitiser Loaded Bacterial Outer Membrane Vesicles Potentiate Antitumour Immunity and Immunotherapy 纳米体工程和光敏剂负载细菌外膜囊泡增强抗肿瘤免疫和免疫治疗

IF 15.5 1区医学

Journal of Extracellular Vesicles Pub Date : 2025-04-16 DOI: 10.1002/jev2.70069

Peng Xia, Chengming Qu, Xiaolong Xu, Ming Tian, Zhifen Li, Jingbo Ma, Rui Hou, Han Li, Felix Rückert, Tianyu Zhong, Liang Zhao, Yufeng Yuan, Jigang Wang, Zhijie Li

{"title":"Nanobody Engineered and Photosensitiser Loaded Bacterial Outer Membrane Vesicles Potentiate Antitumour Immunity and Immunotherapy","authors":"Peng Xia, Chengming Qu, Xiaolong Xu, Ming Tian, Zhifen Li, Jingbo Ma, Rui Hou, Han Li, Felix Rückert, Tianyu Zhong, Liang Zhao, Yufeng Yuan, Jigang Wang, Zhijie Li","doi":"10.1002/jev2.70069","DOIUrl":"https://doi.org/10.1002/jev2.70069","url":null,"abstract":"Bacterial outer membrane vesicles (OMVs) are promising as antitumour agents, but their clinical application is limited by toxicity concerns and unclear mechanisms. We engineered OMVs with cadherin 17 (CDH17) tumour-targeting nanobodies, enhancing tumour selectivity and efficacy while reducing adverse effects. These engineered OMVs function as natural stimulator of interferon genes (STING) agonists, activating the cyclic GMP-AMP synthase (cGAS)-STING pathway in cancer cells and tumour-associated macrophages (TAMs). Loading engineered OMVs with photoimmunotherapy photosensitisers further enhanced tumour inhibition and STING activation in TAMs. Combining nanobody-engineered OMV-mediated photoimmunotherapy with CD47 blockade effectively suppressed primary and metastatic tumours, establishing sustained antitumour immune memory. This study demonstrates the potential of nanobody-engineered OMVs as STING agonists and provides insights into novel OMV-based immunotherapeutic strategies harnessing the innate immune system against cancer. Our findings open new avenues for OMV applications in tumour immunotherapy, offering a promising approach to overcome current limitations in cancer treatment.","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Fusobacterium nucleatum-Derived Outer Membrane Vesicles Promote Immunotherapy Resistance via Changes in Tryptophan Metabolism in Tumour-Associated Macrophages 核酸分枝杆菌衍生的外膜囊泡通过改变肿瘤相关巨噬细胞的色氨酸代谢促进免疫疗法抵抗力

IF 15.5 1区医学

Journal of Extracellular Vesicles Pub Date : 2025-04-16 DOI: 10.1002/jev2.70070

Weiping Li, Zhen Zhang, Ruoyi Wu, Mengying Mao, Yikang Ji, Xiaoning Wang, Shengjin Dou, Ming Yan, Wantao Chen

{"title":"Fusobacterium nucleatum-Derived Outer Membrane Vesicles Promote Immunotherapy Resistance via Changes in Tryptophan Metabolism in Tumour-Associated Macrophages","authors":"Weiping Li, Zhen Zhang, Ruoyi Wu, Mengying Mao, Yikang Ji, Xiaoning Wang, Shengjin Dou, Ming Yan, Wantao Chen","doi":"10.1002/jev2.70070","DOIUrl":"https://doi.org/10.1002/jev2.70070","url":null,"abstract":"Only a minority of patients with head and neck squamous cell carcinoma (HNSCC) respond favourably to immunotherapy. The oral oncogenic bacterium Fusobacterium nucleatum (F.nucleatum) was recently observed to suppress the anti-tumour immune response, although the mechanisms remain unclear. In this study, we found that outer membrane vesicles (OMVs) derived from F.nucleatum (F.n-OMVs) promoted HNSCC progression by inducing immunosuppressive phenotypes of tumour-associated macrophages (TAMs), resulting in decreased cytotoxic T lymphocyte infiltration in vivo. Mechanistically, TAMs internalized tryptophanase presented in F.n-OMVs, which activated the tryptophan-2,3-dioxygenase 2/aryl hydrocarbon receptor (TDO2/AHR) pathway and upregulated the transcription of immunosuppressive cytokines and immune checkpoints. TDO2 inhibitor enhanced the therapeutic effect of anti-programmed death-1 in a tumour-bearing mouse model. Both TDO2 and F.nucleatum demonstrated excellent performance in predicting the immunotherapy outcomes in patients with HNSCC. These results indicate that F.n-OMVs induce immunotherapy resistance in HNSCC, providing novel insights into the microbiota–tumour immunity crosstalk.","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Use of the Malaria Protein VAR2CSA for the Detection of Small Extracellular Vesicles to Diagnose Adenocarcinoma 应用疟疾蛋白VAR2CSA检测细胞外小泡诊断腺癌

IF 15.5 1区医学

Journal of Extracellular Vesicles Pub Date : 2025-04-16 DOI: 10.1002/jev2.70067

Yaru Zhao, Chenlei Wen, Qi Wang, Yue Qing, Serena Tondi, Chiara Reina, Berina Šabanović, Cherry Yin-Yi Chang, Chu-Hu Lai, Huimin Wang, Mette Ø. Agerbaek, Thomas M. Clausen, Tobias Gustavsson, Thor G. Theander, Ali Salanti, Clara Csilla Meny, Baiyong Shen, Alexandra Aicher, Jiajia Tang, Christopher Heeschen

{"title":"Use of the Malaria Protein VAR2CSA for the Detection of Small Extracellular Vesicles to Diagnose Adenocarcinoma","authors":"Yaru Zhao, Chenlei Wen, Qi Wang, Yue Qing, Serena Tondi, Chiara Reina, Berina Šabanović, Cherry Yin-Yi Chang, Chu-Hu Lai, Huimin Wang, Mette Ø. Agerbaek, Thomas M. Clausen, Tobias Gustavsson, Thor G. Theander, Ali Salanti, Clara Csilla Meny, Baiyong Shen, Alexandra Aicher, Jiajia Tang, Christopher Heeschen","doi":"10.1002/jev2.70067","DOIUrl":"https://doi.org/10.1002/jev2.70067","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge for early diagnosis due to the lack of sensitive and specific biomarkers. This encouraged us to explore the diagnostic value of cancer-derived small extracellular vesicles (sEVs) as early detection biomarkers. We previously showed that the recombinant malaria protein VAR2CSA (rVAR2) selectively binds to oncofetal chondroitin sulfate (ofCS) on the surfaces of cancer cells, which might be useful for identifying cancer-derived sEVs. Indeed, flow cytometry revealed strong ofCS expression in PDAC cell-derived sEVs, as evidenced by the presence of mutant KRAS, a common genetic alteration in PDAC. Plasma from PDAC patients showed significantly higher ofCS+ sEV levels compared to healthy donors and patients with benign gastrointestinal diseases. ROC analysis for ofCS+ sEVs revealed an AUC of 0.9049 for the detection of all-stage and 0.9222 for early-stage PDAC. Notably, mutant KRAS was also detected in these patient-derived sEVs. Most intriguingly, combining ofCS+ sEVs and CA19-9 resulted in an AUC of 0.9707 for the detection of early PDAC. Our study demonstrates that rVAR2 is suitable for detecting ofCS+ cancer-derived sEVs in plasma, thereby providing high efficiency for identifying PDAC patients among a diverse population. These findings suggest that rVAR2-based sEV detection could serve as a powerful diagnostic tool to improve patient survival through early detection.","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Yersinia pestis Actively Inhibits the Production of Extracellular Vesicles by Human Neutrophils 鼠疫耶尔森菌积极抑制人中性粒细胞胞外囊泡的产生

IF 15.5 1区医学

Journal of Extracellular Vesicles Pub Date : 2025-04-16 DOI: 10.1002/jev2.70074

Katelyn R. Sheneman, Timothy D. Cummins, Michael L. Merchant, Joshua L. Hood, Silvia M. Uriarte, Matthew B. Lawrenz

{"title":"Yersinia pestis Actively Inhibits the Production of Extracellular Vesicles by Human Neutrophils","authors":"Katelyn R. Sheneman, Timothy D. Cummins, Michael L. Merchant, Joshua L. Hood, Silvia M. Uriarte, Matthew B. Lawrenz","doi":"10.1002/jev2.70074","DOIUrl":"https://doi.org/10.1002/jev2.70074","url":null,"abstract":"Yersinia pestis is the etiologic agent of the plague. A hallmark of plague is subversion of the host immune response by disrupting host signalling pathways required for inflammation. This non-inflammatory environment permits bacterial colonization and has been shown to be essential for disease manifestation. Previous work has shown that Y. pestis inhibits phagocytosis and degranulation by neutrophils. Manipulation of these key vesicular trafficking pathways suggests that Y. pestis influences extracellular vesicle (EV) secretion, cargo selection, trafficking and/or maturation. Our goals were to define the EV population produced by neutrophils in response to Y. pestis and determine how these vesicles might influence inflammation. Towards these goals, EVs were isolated from human neutrophils infected with Y. pestis or a mutant lacking bacterial effector proteins known to manipulate host cell signalling. Mass spectrometry data revealed that cargoes packaged in EVs isolated from mutant infected cells were enriched with antimicrobial and cytotoxic proteins, contents which differed from uninfected and Y. pestis infected cells. Further, EVs produced in response to Y. pestis lacked inflammatory properties observed in those isolated from neutrophils responding to the mutant. Together, these data demonstrate that Y. pestis actively inhibits the production of antimicrobial EVs produced by neutrophils, likely contributing to immune evasion.","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Extracellular Vesicles Alter Trophoblast Function in Pregnancies Complicated by COVID-19 细胞外囊泡改变妊娠合并COVID-19的滋养细胞功能

IF 15.5 1区医学

Journal of Extracellular Vesicles Pub Date : 2025-04-10 DOI: 10.1002/jev2.70051

Thea N. Golden, Sneha Mani, Rebecca L. Linn, Rita Leite, Natalie A. Trigg, Annette Wilson, Lauren Anton, Monica Mainigi, Colin C. Conine, Brett A. Kaufman, Jerome F. Strauss III, Samuel Parry, Rebecca A. Simmons

{"title":"Extracellular Vesicles Alter Trophoblast Function in Pregnancies Complicated by COVID-19","authors":"Thea N. Golden, Sneha Mani, Rebecca L. Linn, Rita Leite, Natalie A. Trigg, Annette Wilson, Lauren Anton, Monica Mainigi, Colin C. Conine, Brett A. Kaufman, Jerome F. Strauss III, Samuel Parry, Rebecca A. Simmons","doi":"10.1002/jev2.70051","DOIUrl":"https://doi.org/10.1002/jev2.70051","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and resulting coronavirus disease (COVID-19) cause placental dysfunction, which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests that pathophysiology associated with maternal COVID-19, rather than direct placental infection, is responsible for placental dysfunction. We hypothesized that maternal circulating extracellular vesicles (EVs), altered by COVID-19 during pregnancy, contribute to placental dysfunction. To examine this hypothesis, we characterized circulating EVs from pregnancies complicated by COVID-19 and tested their effects on trophoblast cell physiology in vitro. Trophoblast exposure to EVs isolated from patients with an active infection (AI), but not controls, altered key trophoblast functions including hormone production and invasion. Thus, circulating EVs from participants with an AI, both symptomatic and asymptomatic cases, can disrupt vital trophoblast functions. EV cargo differed between participants with COVID-19, depending on the gestational timing of infection, and Controls, which may contribute to the disruption of the placental transcriptome and morphology. Our findings show that COVID-19 can have effects throughout pregnancy on circulating EVs, and circulating EVs are likely to participate in placental dysfunction induced by COVID-19.","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 4","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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