European Journal of Immunology最新文献

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Aging and Viral Evolution Impair Immunity Against Dominant Pan-Coronavirus-Reactive T Cell Epitope 衰老和病毒进化损害对显性泛冠状病毒反应性T细胞表位的免疫
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2025-07-28 DOI: 10.1002/eji.202551888
Lucie Loyal, Karsten Jürchott, Ulf Reimer, Lil Meyer-Arndt, Larissa Henze, Norbert Mages, Jak Kostrzanowski, Bernhard Reus, Maike Mangold, Beate Kruse, Manuela Dingeldey, Birgit Sawitzki, Janine Michel, Marica Grossegesse, Karsten Schnatbaum, Holger Wenschuh, Andreas Nitsche, Nils Lachmann, Bernd Timmermann, Claudia Giesecke-Thiel, Julian Braun, Florian Kern, Andreas Thiel
{"title":"Aging and Viral Evolution Impair Immunity Against Dominant Pan-Coronavirus-Reactive T Cell Epitope","authors":"Lucie Loyal,&nbsp;Karsten Jürchott,&nbsp;Ulf Reimer,&nbsp;Lil Meyer-Arndt,&nbsp;Larissa Henze,&nbsp;Norbert Mages,&nbsp;Jak Kostrzanowski,&nbsp;Bernhard Reus,&nbsp;Maike Mangold,&nbsp;Beate Kruse,&nbsp;Manuela Dingeldey,&nbsp;Birgit Sawitzki,&nbsp;Janine Michel,&nbsp;Marica Grossegesse,&nbsp;Karsten Schnatbaum,&nbsp;Holger Wenschuh,&nbsp;Andreas Nitsche,&nbsp;Nils Lachmann,&nbsp;Bernd Timmermann,&nbsp;Claudia Giesecke-Thiel,&nbsp;Julian Braun,&nbsp;Florian Kern,&nbsp;Andreas Thiel","doi":"10.1002/eji.202551888","DOIUrl":"https://doi.org/10.1002/eji.202551888","url":null,"abstract":"<p>Immune evasion by escape mutations subverts immunity against SARS-CoV-2. A role of pan-coronavirus immunity for more durable protection is being discussed, but has remained understudied. We here investigated the effects of age, mutations, and homo-/heterologous vaccination regimens on the dominant pan-coronavirus-specific cellular and humoral epitope iCope after SARS-CoV-2 infection and vaccination in detail. In older individuals, the quantitatively and qualitatively reduced iCope-reactive CD4<sup>+</sup> T cell responses with narrow TCR repertoires could not be enhanced by vaccination and were further compromised by emerging spike mutations. In contrast, pan-coronavirus-reactive humoral immunity was affected only by mutations and not by age. Our results reveal a distinct deficiency of the dichotomous layer of pan-coronavirus immunity in the older, critical for long-term protection against SARS-CoV-2 variants.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202551888","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunogenicity-Guided Design of an Acinetobacter baumanii Vaccine 免疫原性导向的鲍曼不动杆菌疫苗设计
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2025-07-28 DOI: 10.1002/eji.70019
Chenghua Zhu, Shuaiyuan Liang, Ning Yang, Shan Li, Jianpeng Xue, Runlu Zhou, Xiuwen Hong, Sixi Chen, Nan Gao, Qiang Du, Jianling Huang, Ganzhu Feng, Xingran Du
{"title":"Immunogenicity-Guided Design of an Acinetobacter baumanii Vaccine","authors":"Chenghua Zhu,&nbsp;Shuaiyuan Liang,&nbsp;Ning Yang,&nbsp;Shan Li,&nbsp;Jianpeng Xue,&nbsp;Runlu Zhou,&nbsp;Xiuwen Hong,&nbsp;Sixi Chen,&nbsp;Nan Gao,&nbsp;Qiang Du,&nbsp;Jianling Huang,&nbsp;Ganzhu Feng,&nbsp;Xingran Du","doi":"10.1002/eji.70019","DOIUrl":"https://doi.org/10.1002/eji.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>The development of vaccines represents a promising and safe strategy to combat multidrug-resistant (MDR) <i>Acinetobacter baumannii</i> (<i>A. baumannii</i>) infections. In this study, we designed and evaluated a dendritic cell (DC)-targeting multiepitope peptide-based biomimetic nanovaccine for its immunogenicity and protective efficacy in a murine model. Bioinformatics tools were employed to predict and screen B- and T-cell epitopes derived from the OmpW protein of <i>A. baumannii</i>, followed by immunological validation. The dominant epitopes were sequentially linked using 6-aminocaproic acid to synthesize a multiepitope peptide, rOmpW. Subsequently, rOmpW was encapsulated within polylactic-co-glycolic acid (PLGA) nanoparticles coated with neutrophil membranes (NM), and the surface was functionalized with a DC-targeting peptide (DCpep) to construct the biomimetic nanovaccine, DCpep-NM-PLGA-rOmpW. This biomimetic nanovaccine elicited robust Th1 and Th17 cellular immune responses, as well as humoral immunity, and demonstrated significant protective efficacy in a murine model of acute lethal pneumonia caused by <i>A. baumannii</i>. These findings underscore the translational potential of this biomimetic nanovaccine as a prophylactic strategy against <i>A. baumannii</i> infections.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716984","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}
引用次数: 0
Machine Learning Reassessment of Serum Immune Factors Shows No Unique Immune Profiles Linked to Disease Outcomes in SARS-CoV-2-infected Patients at Hospital Admittance 机器学习对血清免疫因子的重新评估显示入院时sars - cov -2感染患者的疾病结局没有独特的免疫特征
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2025-07-25 DOI: 10.1002/eji.70001
Stefania Rossi, Imerio Capone, Enrico Cabri, Anna Giabelli, Ilaria Rossoni, Giulia Romagnoli, Stefano M. Santini, Cinzia Marcantonio, Roberto Giuseppetti, Umbertina Villano, Roberto Bruni, Anna R. Ciccaglione, Federica Frasca, Alessandra d'Auria, Ginevra Bugani, Gabriella d'Ettorre, Guido Antonelli, Carolina Scagnolari, Maddalena Fratelli, Lucia Gabriele
{"title":"Machine Learning Reassessment of Serum Immune Factors Shows No Unique Immune Profiles Linked to Disease Outcomes in SARS-CoV-2-infected Patients at Hospital Admittance","authors":"Stefania Rossi,&nbsp;Imerio Capone,&nbsp;Enrico Cabri,&nbsp;Anna Giabelli,&nbsp;Ilaria Rossoni,&nbsp;Giulia Romagnoli,&nbsp;Stefano M. Santini,&nbsp;Cinzia Marcantonio,&nbsp;Roberto Giuseppetti,&nbsp;Umbertina Villano,&nbsp;Roberto Bruni,&nbsp;Anna R. Ciccaglione,&nbsp;Federica Frasca,&nbsp;Alessandra d'Auria,&nbsp;Ginevra Bugani,&nbsp;Gabriella d'Ettorre,&nbsp;Guido Antonelli,&nbsp;Carolina Scagnolari,&nbsp;Maddalena Fratelli,&nbsp;Lucia Gabriele","doi":"10.1002/eji.70001","DOIUrl":"https://doi.org/10.1002/eji.70001","url":null,"abstract":"<p>The complex pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves a hyperinflammatory state with excessive cytokine production, leading to an influenza-like syndrome that may need emergency care. The severity of SARS-CoV-2 varies widely, and collective serum immune factors, evaluated in emergency care patients, have not been shown to correlate with disease progression. We applied a machine learning approach to reassess and define serum immune profiles that could align with clinical laboratory parameters and predict disease outcomes in patients with respiratory virus infections, including those with SARS-CoV-2, seeking emergency care. Sixty-two plasma immune molecules, in a cohort of 67 symptomatic SARS-CoV-2, were analyzed for correlation with antibodies (Abs) to spike (S) and nucleocapsid (N) proteins, as well as with clinical laboratory parameters, to identify early indicators of disease prognosis at hospital admission. This approach allowed us to analyze and cluster unlabeled datasets, delineating three distinct serum immune signatures. Two showed significant and opposite modulations, correlating with poorer disease outcomes, while most patients with moderate disease displayed modest immune factor dysregulation. This highlights the complexity of immune responses in the severity of diseases caused by highly respiratory pathogenic virus like SARS-CoV-2, emphasizing the importance of evaluating overall immune imbalance rather than focusing on a few dysregulated factors.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Platelet-Based Nanotechnology Improves Cancer Immunotherapy 基于血小板的纳米技术改善癌症免疫治疗
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2025-07-24 DOI: 10.1002/eji.70017
Yanlin Lv, Guanghui Ma
{"title":"Platelet-Based Nanotechnology Improves Cancer Immunotherapy","authors":"Yanlin Lv,&nbsp;Guanghui Ma","doi":"10.1002/eji.70017","DOIUrl":"https://doi.org/10.1002/eji.70017","url":null,"abstract":"<p>Cancer immunotherapy is a cornerstone of precision medicine, yet its efficacy is often hampered by the immunosuppressive and heterogeneous microenvironment of solid tumors. Biomimetic nanodelivery systems have emerged as promising tools to enhance therapeutic outcomes while minimizing off-target effects. Among these, platelet (PLT)-based systems offer unique advantages, including prolonged circulation, immune evasion, and tumor-targeting capabilities. Of particular value is their ability to localize to sites of injury, which is a feature that nanocarriers cannot achieve. This review explores the multifaceted role of platelets in tumor development and metastasis, highlighting their bidirectional interactions with tumors. It further discusses the application of PLT-based nanotechnology in cancer immunotherapy, emphasizing recent advancements in immune regulation, targeted therapy, and clinical translation. We also address the challenges and considerations in developing PLT-based platforms, outlining future directions for their optimization in cancer treatment.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Self-Antigens Select B Cells: A New Perspective on B Cell Selection and Function 自体抗原选择B细胞:B细胞选择和功能的新视角
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2025-07-22 DOI: 10.1002/eji.202451720
Mike Aoun, Rikard Holmdahl
{"title":"Self-Antigens Select B Cells: A New Perspective on B Cell Selection and Function","authors":"Mike Aoun,&nbsp;Rikard Holmdahl","doi":"10.1002/eji.202451720","DOIUrl":"https://doi.org/10.1002/eji.202451720","url":null,"abstract":"<p>The adaptive immune system is shaped by self-recognition, creating a paradox where autoreactivity is essential for immune regulation, yet implicated in autoimmune diseases. Traditionally, B cell selection in the bone marrow (BM) has been viewed through the lens of negative selection, eliminating potentially harmful clones. Emerging evidence challenges this perspective, revealing a subset of B suppressor cells (Bsup) that actively regulate immune homeostasis. Unlike conventional negative selection, C1-specific Bsup cells, which recognize collagen type II (Col2), engage Col2-specific regulatory T cells (Tregs) to suppress inflammation in healthy individuals. This suggests that Bsup play a role in both peripheral and central tolerance, akin to Tregs. However, the molecular mechanisms governing Bsup selection, differentiation, and function remain unknown. Understanding how Bsup distinguish homeostatic from pathogenic autoreactivity could transform autoimmune disease treatment, shifting the focus from eliminating autoreactive B cells to harnessing their regulatory potential for precision immunotherapy.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Homeobox Transcription Factor HOXB4 Distinctly Modulates Th2 and Th9 Cell Differentiation 同源盒转录因子HOXB4明显调节Th2和Th9细胞分化
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2025-07-20 DOI: 10.1002/eji.202451752
Shagnik Chattopadhyay, Sayantee Hazra, Biswajit Biswas, Ritobrata Goswami
{"title":"Homeobox Transcription Factor HOXB4 Distinctly Modulates Th2 and Th9 Cell Differentiation","authors":"Shagnik Chattopadhyay,&nbsp;Sayantee Hazra,&nbsp;Biswajit Biswas,&nbsp;Ritobrata Goswami","doi":"10.1002/eji.202451752","DOIUrl":"https://doi.org/10.1002/eji.202451752","url":null,"abstract":"<div>\u0000 \u0000 <p>CD4+ T helper cells are involved in multiple biological processes ranging from pathogen clearance to immune tolerance. Differentiation of CD4+ T cells into varied subsets is dependent on transcription factors, cytokines, micronutrients, and epigenetic modifications. Here, we report the molecular mechanisms imparted by the homeobox transcription factor HOXB4 in modulating Th2 and Th9 cell differentiation. We found that <i>Hoxb4</i> induction in T helper cells was TGF-β-dependent. In Th9 cells, HOXB4 overexpression significantly increased IL-9 secretion, while in Th2 cells, HOXB4 could alter only IL-10 secretion among other type 2 cytokines. Promoter activity analyses revealed that HOXB4 was able to transactivate the <i>Il9</i> and <i>Il10</i> proximal promoters, while the <i>Il4</i> and <i>Il13</i> promoters were differentially modulated. We observed that HOXB4 could physically interact with the transcription factor PU.1 but not GATA3, and directly bind PU.1 response element on the DNA in Th9 cells. The recruitment of HOXB4 was found to be significantly increased in regulatory regions including cECR and CNS1 (<i>Il9</i> promoter). Collectively, our findings suggest that HOXB4 works downstream of the TGF-β signalling pathway, associates with PU.1, binds the regulatory regions, and distinctly regulates both Th2 and Th9 cell differentiation.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666455","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}
引用次数: 0
Teriflunomide Inhibits Human FOXP3+ Regulatory T Cell Function by Interference With Mitochondrial Respiration 特立氟米特通过干扰线粒体呼吸抑制人FOXP3+调节性T细胞功能
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2025-07-20 DOI: 10.1002/eji.202451260
Aleksandra Dyczko, Beatriz F. Côrte-Real, Ibrahim Hamad, Ralf A. Linker, Markus Kleinewietfeld
{"title":"Teriflunomide Inhibits Human FOXP3+ Regulatory T Cell Function by Interference With Mitochondrial Respiration","authors":"Aleksandra Dyczko,&nbsp;Beatriz F. Côrte-Real,&nbsp;Ibrahim Hamad,&nbsp;Ralf A. Linker,&nbsp;Markus Kleinewietfeld","doi":"10.1002/eji.202451260","DOIUrl":"https://doi.org/10.1002/eji.202451260","url":null,"abstract":"<div>\u0000 \u0000 <p>Regulatory FOXP3<sup>+</sup> T cells (Tregs) have been characterized with unique metabolic demands, preferentially relying on fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS). Several studies have indicated that Treg mitochondrial fitness is crucial for maintaining their stability and suppressive activity with an emphasis on complex-III of the electron transport chain (ETC). Dysfunctional Tregs isolated from patients with autoimmunity like multiple sclerosis (MS) show diminished mitochondrial respiration and the induction of a T helper (Th)1-like phenotype, characterized by increased production of interferon (IFN)-γ. Teriflunomide reduces the proliferation of activated T and B lymphocytes by inhibition of de novo pyrimidine synthesis, providing therapy for patients with autoimmune diseases. Recent data demonstrated that teriflunomide further inhibited complex-III activity in line with hampered mitochondrial respiration in T cells. Considering the essential role of OXPHOS and complex-III activity for Tregs, we therefore thought to investigate with this study the effects of teriflunomide on immunometabolism and function in human Tregs. Interestingly, teriflunomide impaired the mitochondrial function of human Tregs and further induced a Th1-like phenotype in line with defective suppressive activity. Our findings suggest that teriflunomide may potentially exert distinct effects on pro- versus anti-inflammatory T cell subsets, indicating the need for further detailed evaluation.</p>\u0000 </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666456","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}
引用次数: 0
The Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment 肿瘤糖密码:唾液酰化作为肿瘤微环境中基质细胞免疫抑制的中介
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2025-07-16 DOI: 10.1002/eji.70000
Aoise O'Neill, Norashikin Zakaria, Hannah Egan, Oliver Treacy, Aisling M. Hogan, Michael O'Dwyer, Sean O. Hynes, Aideen E. Ryan
{"title":"The Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment","authors":"Aoise O'Neill,&nbsp;Norashikin Zakaria,&nbsp;Hannah Egan,&nbsp;Oliver Treacy,&nbsp;Aisling M. Hogan,&nbsp;Michael O'Dwyer,&nbsp;Sean O. Hynes,&nbsp;Aideen E. Ryan","doi":"10.1002/eji.70000","DOIUrl":"https://doi.org/10.1002/eji.70000","url":null,"abstract":"<p>The tumour microenvironment (TME) comprises a complex interplay of tumour cells, nonmalignant cells (including endothelial, immune, and stromal cells), and secreted factors within the extracellular matrix (ECM). Immunosuppression within the TME significantly hinders the efficacy of cancer immunotherapies. Stromal-rich TMEs, characterised by an abundance of mesenchymal stromal cells (MSCs) and cancer-associated fibroblasts (CAFs), are particularly immunosuppressive and associated with poor responses to conventional and immune-based therapies. Glycans, carbohydrate structures on cell surfaces, are dynamically regulated during tumourigenesis and mediate crucial cell–cell communications through receptor–ligand interactions. Sialylation, the addition of sialic acids to glycans, forms sialoglycans that can engage inhibitory Siglec receptors expressed on immune cells and promote immunosuppressive signalling. Emerging evidence implicates aberrant sialylation in the TME as a key driver of immunosuppression. More recently, sialylation of stromal cells in the TME has been shown to suppress anti-tumor immunity. This review explores the role of sialylation within stromal-rich, immunosuppressive TMEs, focusing on how specific sialic acid/Siglec interactions dictate innate and adaptive immune responses. We discuss the potential of targeting glycoimmune checkpoints to overcome stromal-mediated resistance and enhance anti-tumour immunity.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fever-Induced Heat Shock Protein-70 Regulates Macrophage IL-1β and IL-10 Secretion During Mycobacterium tuberculosis Infection 热休克蛋白70调控结核分枝杆菌感染时巨噬细胞IL-1β和IL-10的分泌
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2025-07-16 DOI: 10.1002/eji.202551963
Deborah L. W. Chong, Sajeel A. Shah, Julia Kutschenreuter, Ramla Cusman, Meena Murugananden Pillai, Daniela E. Kirwan, Robert H. Gilman, Jon S. Friedland
{"title":"Fever-Induced Heat Shock Protein-70 Regulates Macrophage IL-1β and IL-10 Secretion During Mycobacterium tuberculosis Infection","authors":"Deborah L. W. Chong,&nbsp;Sajeel A. Shah,&nbsp;Julia Kutschenreuter,&nbsp;Ramla Cusman,&nbsp;Meena Murugananden Pillai,&nbsp;Daniela E. Kirwan,&nbsp;Robert H. Gilman,&nbsp;Jon S. Friedland","doi":"10.1002/eji.202551963","DOIUrl":"https://doi.org/10.1002/eji.202551963","url":null,"abstract":"<p>Fever is a common clinical symptom in patients with tuberculosis (TB). During fever, heat-shock proteins (HSPs), such as HSP70, are expressed, which are molecular chaperones regulating protein folding and may also have immunomodulatory properties. How fever modulates immune responses during TB and by which mechanisms is unknown. In this study, we investigated the effects of fever, and specifically the role of HSP70, on <i>Mycobacterium tuberculosis</i> (<i>Mtb)</i>-induced macrophage inflammatory responses. Human monocyte-derived macrophages (MDM) were infected with <i>Mtb</i> at 37°C or 40°C to mimic febrile conditions. Fever suppresses <i>Mtb</i>-induced IL-1β and IL-10 gene expression and secretion from MDM, but enhances <i>Mtb</i>-induced HSP70 secretion and intracellular accumulation in MDM. Extracellular HSP70 and HSP70-expressing macrophages are abundant in granulomas in TB patient biopsies. HSP70 antagonism decreases <i>Mtb</i>-induced IL-1β secretion during febrile conditions but has no significant effect on IL-10 secretion. Pretreatment of MDM with recombinant HSP70 significantly increases <i>Mtb</i>-induced IL-1β at 37°C. Finally, extracellular HSP70 negatively regulates further HSP70 secretion from MDM during <i>Mtb</i> infection. Overall, fever and subsequent HSP70 expression modulates proinflammatory innate immune response in TB, which may have implications for the development of host-directed therapies.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202551963","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
T Cell Response Evaluation After A Fifth Dose of an Inactivated SARS-CoV-2 Vaccine Using Multiparametric Flow Cytometry 使用多参数流式细胞术评估第五剂灭活疫苗后的T细胞反应
IF 4.5 3区 医学
European Journal of Immunology Pub Date : 2025-07-16 DOI: 10.1002/eji.202551848
Francisca Román, Antonia Reyes, Cristián Gutiérrez, Linmar Rodríguez-Guilarte, Constanza Méndez, Daniela Moreno-Tapia, Mariana Ríos, Alex Cabrera, Leandro J. Carreño, Pablo A. González, Susan M. Bueno, Alexis M. Kalergis, Hernán F. Peñaloza
{"title":"T Cell Response Evaluation After A Fifth Dose of an Inactivated SARS-CoV-2 Vaccine Using Multiparametric Flow Cytometry","authors":"Francisca Román,&nbsp;Antonia Reyes,&nbsp;Cristián Gutiérrez,&nbsp;Linmar Rodríguez-Guilarte,&nbsp;Constanza Méndez,&nbsp;Daniela Moreno-Tapia,&nbsp;Mariana Ríos,&nbsp;Alex Cabrera,&nbsp;Leandro J. Carreño,&nbsp;Pablo A. González,&nbsp;Susan M. Bueno,&nbsp;Alexis M. Kalergis,&nbsp;Hernán F. Peñaloza","doi":"10.1002/eji.202551848","DOIUrl":"https://doi.org/10.1002/eji.202551848","url":null,"abstract":"<p>The T cell response induced by SARS-CoV-2 vaccines is an essential component of immune protection against COVID-19. Multiparametric flow cytometry analysis emerges as a valuable tool for in-depth assessment of T cell phenotype nuances that occur after booster vaccination, such as a fifth dose of an inactivated SARS-CoV-2 vaccine. Figure created with BioRender.com.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634977","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}
引用次数: 0
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