Journal of immunology最新文献

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The MicroRNA miR-223 Constrains Colitis-associated Tumorigenesis by Limiting Myeloid Cell Infiltration and Chemokine Expression. 微小RNA miR-223通过限制髓系细胞浸润和趋化因子表达制约结肠炎相关肿瘤发生
IF 3.6 3区 医学
Journal of immunology Pub Date : 2024-11-01 DOI: 10.4049/jimmunol.2400129
Ciara L Flynn, Gary E Markey, Viola Neudecker, Charlotte Farrelly, Glenn T Furuta, Holger K Eltzschig, Joanne C Masterson, Eóin N McNamee
{"title":"The MicroRNA miR-223 Constrains Colitis-associated Tumorigenesis by Limiting Myeloid Cell Infiltration and Chemokine Expression.","authors":"Ciara L Flynn, Gary E Markey, Viola Neudecker, Charlotte Farrelly, Glenn T Furuta, Holger K Eltzschig, Joanne C Masterson, Eóin N McNamee","doi":"10.4049/jimmunol.2400129","DOIUrl":"https://doi.org/10.4049/jimmunol.2400129","url":null,"abstract":"<p><p>Aberrant intestinal inflammation plays a critical role in the development of colitis-associated colorectal cancer (CAC), yet the mechanisms controlling tumor development by the myeloid immune compartment are not fully understood. Although altered microRNA expression is observed in CAC, it is also unclear how myeloid-specific microRNAs impact the inflammatory process that underpins the continuum from ulcerative colitis to tumorigenesis. In this study, we report that miR-223 acts to limit myeloid-driven inflammation in the azoxymethane (AOM)-dextran sodium sulfate (DSS) model of CAC in mice. In this model, miR-223-/y mice present with significantly larger tumors with an enhanced proliferative signature. Immunoprofiling showed that miR-223-/y mice have significantly increased colonic myeloid immune infiltrate (neutrophils, monocytes, and macrophages) following AOM-DSS. This was accompanied by an increased inflammatory chemokine and cytokine signature for monocytes and neutrophils. Bone marrow chimera studies demonstrate that myeloid-expressed miR-223 is responsible for the enhanced tumor proliferation and inflammatory response. RNA sequencing identified several pathways that could be contributing to the development of CAC in miR-223-/y mice, including the IL-6/IL-17a cytokine family and STAT3 signaling. Lastly, neutrophil depletion with an anti-GR1 Ab (Ly6G/Ly6C) during the initial phase of the AOM-DSS model reduced the tumor burden in miR-223-/y mice. Collectively, our data indicate that miR-223 is an important regulator of mucosal inflammation and acts to constrain the progression from ulcerative colitis to CAC by limiting myeloid-associated inflammation.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558062","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
Regulation and Dynamics of IFN-β Expression Revealed with a Knockin Reporter Mouse. 用基因敲除报告小鼠揭示 IFN-β 表达的调控和动态变化
IF 3.6 3区 医学
Journal of immunology Pub Date : 2024-10-30 DOI: 10.4049/jimmunol.2400227
Nikhil J Parekh, Damion Winship, Erik Van Dis, Daniel B Stetson
{"title":"Regulation and Dynamics of IFN-β Expression Revealed with a Knockin Reporter Mouse.","authors":"Nikhil J Parekh, Damion Winship, Erik Van Dis, Daniel B Stetson","doi":"10.4049/jimmunol.2400227","DOIUrl":"https://doi.org/10.4049/jimmunol.2400227","url":null,"abstract":"<p><p>IFN-β is a potent antiviral cytokine and the first member of the type I IFN family of cytokines to be induced during the antiviral response. IFN-β plays an essential protective role in host defense against virus infections, as well as a pathogenic role in numerous autoimmune and autoinflammatory disorders. However, contemporary tools to study the induction, kinetics, and behavior of IFN-β are lacking. In this study, we describe a knockin Ifnb-IRES-TdTomato-Cre reporter mouse to track IFN-β-expressing cells. We demonstrate pathway-specific induction of the TdTomato reporter and show that the linked Cre recombinase enables permanent marking of cells that express IFN-β. We identify a robust MAVS-dependent IFN-β response in lung epithelial cells following Sendai virus infection in vivo. Finally, we find that activation of RNase L in macrophages by RNA ligands of the RIG-I-like receptors prevents protein translation of IFN-β and the TdTomato reporter. Our mouse model provides a powerful tool to study the biology of type I IFN induction and the antiviral response.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545872","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
Neonatal Neutrophil-mediated Control of Bordetella pertussis Is Disrupted by Pertussis Toxin. 新生儿中性粒细胞介导的百日咳杆菌控制被百日咳毒素破坏
IF 3.6 3区 医学
Journal of immunology Pub Date : 2024-10-30 DOI: 10.4049/jimmunol.2400363
Colleen J Sedney, Jillian Masters, Maiya Callender, Kalyan Dewan, Amanda Caulfield, Eric T Harvill
{"title":"Neonatal Neutrophil-mediated Control of Bordetella pertussis Is Disrupted by Pertussis Toxin.","authors":"Colleen J Sedney, Jillian Masters, Maiya Callender, Kalyan Dewan, Amanda Caulfield, Eric T Harvill","doi":"10.4049/jimmunol.2400363","DOIUrl":"https://doi.org/10.4049/jimmunol.2400363","url":null,"abstract":"<p><p>The increased susceptibility of infants and young children to some diseases has often been explained as the neonatal immune system (NIS) being incomplete and/or underdeveloped. However, our recent work demonstrated that neonatal mice could clear a Bordetella pertussis (Bp) strain lacking pertussis toxin (PTx) (BpΔptx) much more efficiently than adult mice, indicating that the NIS can be extremely effective, but this ability is highly sensitive to being blocked by PTx. In this article, we investigated immunological mechanisms by which neonates efficiently and rapidly clear BpΔptx to better understand how the NIS functions and how PTx disrupts it. Depleting neutrophils, or blocking their recruitment, inhibited pups' ability to rapidly clear BpΔptx, revealing a critical role for neutrophils. Pups deficient in complement (C3-/-) failed to recruit neutrophils and did not efficiently clear BpΔptx but recovered these abilities upon treatment with C3a. Neutrophil depletion in C3-/- pups led to further failure to control BpΔptx, suggesting that neutrophils and complement have independent roles in rapid clearance of BpΔptx. Depleting or disrupting neutrophils and complement had negligible effect on the rapid growth of wild-type Bp, indicating that PTx blocks these otherwise highly effective aspects of the NIS.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545871","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
Rhesus Macaque Killer Cell Ig-like Receptor Domain 0 Glycans Impact Surface Expression and Ligand Specificity. 猕猴杀伤细胞 Ig 样受体 0 结构域聚糖对表面表达和配体特异性的影响
IF 3.6 3区 医学
Journal of immunology Pub Date : 2024-10-28 DOI: 10.4049/jimmunol.2400466
Jennifer L Anderson, Kjell Sandstrom, Vadim A Klenchin, David T Evans
{"title":"Rhesus Macaque Killer Cell Ig-like Receptor Domain 0 Glycans Impact Surface Expression and Ligand Specificity.","authors":"Jennifer L Anderson, Kjell Sandstrom, Vadim A Klenchin, David T Evans","doi":"10.4049/jimmunol.2400466","DOIUrl":"https://doi.org/10.4049/jimmunol.2400466","url":null,"abstract":"<p><p>Defining the MHC class I ligands of rhesus macaque killer cell Ig-like receptors (KIRs) is fundamental to NK cell biology in this species as a model for infectious diseases and comparative immunogenetics. Several rhesus macaque KIRs belong to a phylogenetically distinct group with a three-amino acid deletion in domain 0 (D0). This deletion results in polymorphic differences in potential N-linked glycosylation (PNG) sites adjacent to a predicted KIR-MHC class I contact site. Whereas most KIRs have two tandem PNG sites in D0 (N36FTN39FT), the KIRs containing the deletion only have a single site in this region (N36FT). To discern the contribution of glycosylation to KIR expression and ligand recognition, we constructed PNG mutants for six lineage II KIR genes that eliminate or create sites for N-glycan addition at these locations. The impact of these mutations on total and surface expression was determined by immunoblotting and flow cytometry. Ligand engagement was assessed by coincubating reporter cell lines bearing chimeric KIR-CD3ζ receptors with target cells expressing individual MHC class I molecules and were corroborated by staining with KIR IgG-Fc fusion proteins. We found that N36FT is glycosylated in KIR with a single site, and at least one site is glycosylated in KIRs with two tandem sites. In general, for rhesus KIRs with a single D0 glycosylation site, that site contributes to surface expression. For KIRs with two tandem sites, the first site can contribute to ligand specificity. This study establishes that D0 glycosylation of rhesus macaque KIRs modulates surface expression and contributes to ligand specificity.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502053","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
Local Controlled Delivery of IL-4 Decreases Inflammatory Bone Loss in a Murine Model of Periodontal Disease. 局部控制性递送 IL-4 可减少小鼠牙周病模型中炎性骨质流失。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2024-10-28 DOI: 10.4049/jimmunol.2400332
Mostafa Shehabeldin, Julie Kobyra, Yejin Cho, Jin Gao, Rong Chong, Tracy Tabib, Robert Lafyatis, Steven R Little, Charles Sfeir
{"title":"Local Controlled Delivery of IL-4 Decreases Inflammatory Bone Loss in a Murine Model of Periodontal Disease.","authors":"Mostafa Shehabeldin, Julie Kobyra, Yejin Cho, Jin Gao, Rong Chong, Tracy Tabib, Robert Lafyatis, Steven R Little, Charles Sfeir","doi":"10.4049/jimmunol.2400332","DOIUrl":"https://doi.org/10.4049/jimmunol.2400332","url":null,"abstract":"<p><p>Chronic inflammatory diseases are a leading global health problem. In many of these diseases, the consistent presence of systemic low-grade inflammation induces tissue damage. This is true in conditions such as diabetes, arthritis, and autoimmune disorders, where an overactive and uncontrolled host immune response is a major driver of immunopathology. Central to this overactive and destructive host response are macrophages, the major phagocytic cells within the innate immune system. These cells exhibit a dual role in both host defense against invading pathogens and promotion of tissue repair during inflammation resolution. Those unique characteristics make macrophages an excellent target for therapeutic interventions in many chronic inflammatory conditions. Using periodontal disease as a model of chronic inflammation, we sought to assess the feasibility of using a controlled drug delivery strategy to target macrophages within the oral cavity. To that end, IL-4 was encapsulated within a biodegradable polymer carrier and locally delivered into the inflamed periodontal tissues. Our data indicate that local sustained delivery of IL-4 decreased inflammatory bone loss and promoted bone gain in the diseased mouse periodontium. Those effects correlated with a shift of local macrophage population toward a prorepair phenotype. Using single-cell RNA sequencing technology, we found that IL-4 delivery reversed several proinflammatory pathways associated with tissue destructive macrophages. Together, our data suggest that sustained delivery of IL-4 may be a viable therapeutic option for chronic diseases characterized by immune-mediated tissue damage.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502051","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
Identification of a Specific Granular Marker of Zebrafish Eosinophils Enables Development of New Tools for Their Study. 鉴定斑马鱼嗜酸性粒细胞的特异性颗粒标记有助于开发研究嗜酸性粒细胞的新工具
IF 3.6 3区 医学
Journal of immunology Pub Date : 2024-10-28 DOI: 10.4049/jimmunol.2400259
Miriam Herbert, Christian Goosmann, Volker Brinkmann, Christiane Dimmler, Mark R Cronan
{"title":"Identification of a Specific Granular Marker of Zebrafish Eosinophils Enables Development of New Tools for Their Study.","authors":"Miriam Herbert, Christian Goosmann, Volker Brinkmann, Christiane Dimmler, Mark R Cronan","doi":"10.4049/jimmunol.2400259","DOIUrl":"https://doi.org/10.4049/jimmunol.2400259","url":null,"abstract":"<p><p>Eosinophils control many aspects of the vertebrate innate immune response. They contribute to homeostasis, inflammatory conditions and defense against pathogens. With the varied functions of eosinophils, they have been found to play both protective and pathogenic roles in many diseases. The zebrafish (Danio rerio) has emerged as a useful model organism for human diseases but tools to study eosinophils in this model are severely limited. Here, we characterize a new and highly specific marker gene, embp, for eosinophils in zebrafish and report a new transgenic reporter line using this gene to visualize eosinophils in vivo. In addition, we created an Embp-specific polyclonal Ab that allows the identification of eosinophils ex vivo. These new tools expand the approaches for studying eosinophils in the zebrafish model. Using these reagents, we have been able to identify Embp as a constituent of eosinophil granules in zebrafish. These advances will allow for the investigation of eosinophil biology in the zebrafish model organism, allowing researchers to identify the contribution of eosinophils to the many diseases that are modeled within zebrafish and also shed light on the evolution of eosinophils within vertebrates.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502049","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
IL-33 Increases the Magnitude of the Tissue-Resident Memory T Cell Response in Intestinal Tissues during Local Infection. IL-33 增加局部感染期间肠道组织中组织驻留记忆 T 细胞反应的幅度
IF 3.6 3区 医学
Journal of immunology Pub Date : 2024-10-28 DOI: 10.4049/jimmunol.2400323
Giuseppina Marchesini Tovar, Angie M Espinal, Corey Gallen, Tessa Bergsbaken
{"title":"IL-33 Increases the Magnitude of the Tissue-Resident Memory T Cell Response in Intestinal Tissues during Local Infection.","authors":"Giuseppina Marchesini Tovar, Angie M Espinal, Corey Gallen, Tessa Bergsbaken","doi":"10.4049/jimmunol.2400323","DOIUrl":"https://doi.org/10.4049/jimmunol.2400323","url":null,"abstract":"<p><p>IL-33 plays an important role in the early programming of CD8 T cells; however, its contribution to the differentiation of tissue-resident memory T cells in vivo remains poorly defined. After infection of mice with Yersinia pseudotuberculosis, IL-33 expression was increased in the intestinal tissue, and this coincided with the expression of ST2 on T cells infiltrating the intestinal epithelium and lamina propria. Blocking IL-33 signaling after T cell infiltration of the intestinal tissue did not significantly impact the number or phenotype of tissue-resident memory T cells generated. However, overexpression of ST2 on T cells was able to increase expression of TCF1 and T cell number in the intestine compared with the lymphoid organs during infection. We also observed that enhanced accumulation and maintenance of ST2-overexpressing cells in the intestine postinfection were resolved. This points to a role for IL-33 in increasing the number of T cells that commit to intestinal tissue residency in vivo.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502050","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
Suppression of Class Switch Recombination to IgA by RASA2 and RASA3 through Inhibition of TGF-β Signaling. RASA2 和 RASA3 通过抑制 TGF-β 信号抑制 IgA 的类转换重组
IF 3.6 3区 医学
Journal of immunology Pub Date : 2024-10-25 DOI: 10.4049/jimmunol.2400353
Sami Mamand, Heather Liu, Mohammad Kashem, Alberto Martin
{"title":"Suppression of Class Switch Recombination to IgA by RASA2 and RASA3 through Inhibition of TGF-β Signaling.","authors":"Sami Mamand, Heather Liu, Mohammad Kashem, Alberto Martin","doi":"10.4049/jimmunol.2400353","DOIUrl":"https://doi.org/10.4049/jimmunol.2400353","url":null,"abstract":"<p><p>Abs play a pivotal role in adaptive immunity by binding to pathogens and initiating immune responses against infections. Processes such as somatic hypermutation and class switch recombination (CSR) enhance Ab affinity and effector functions. We previously carried out a CRISPR/Cas9 screen in the CH12F3-2 (CH12) lymphoma B cell line to identify novel factors involved in CSR. The screen showed that guide RNAs targeting both Rasa2 and Rasa3 genes were decreased in IgA-negative CH12 B cells, implying that these genes might suppress CSR. Indeed, CSR was increased when either Rasa2 or Rasa3 were knocked out in CH12 cells. Compared to controls, Rasa2-/- and Rasa3-/- CH12 cells had increased expression of activation-induced cytidine deaminase (AID) and Iα transcripts, providing an explanation for the increased CSR. The increased CSR, AID, and Iα expression in Rasa2-/- or Rasa3-/- CH12F3-2 is mediated through TGF-β stimulation. Indeed, we found that deletion of RASA2 or RASA3 promotes a shift from noncanonical to canonical TGF-β signaling through SMAD3. These results show that RASA2 and RASA3 are both novel regulators of TGF-β signaling in B cells, a pathway known to be essential for CSR to IgA.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502055","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
Development of a Spectral Flow Cytometry Analysis Pipeline for High-dimensional Immune Cell Characterization. 开发用于高维免疫细胞特征描述的光谱流式细胞仪分析管道。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2024-10-25 DOI: 10.4049/jimmunol.2400370
Donald Vardaman, Md Akkas Ali, Md Hasanul Banna Siam, Chase Bolding, Harrison Tidwell, Holly R Stephens, Mallikarjun Patil, Daniel J Tyrrell
{"title":"Development of a Spectral Flow Cytometry Analysis Pipeline for High-dimensional Immune Cell Characterization.","authors":"Donald Vardaman, Md Akkas Ali, Md Hasanul Banna Siam, Chase Bolding, Harrison Tidwell, Holly R Stephens, Mallikarjun Patil, Daniel J Tyrrell","doi":"10.4049/jimmunol.2400370","DOIUrl":"10.4049/jimmunol.2400370","url":null,"abstract":"<p><p>Flow cytometry is used for immune cell analysis for cell composition and function. Spectral flow cytometry allows for high-dimensional analysis of immune cells, overcoming limitations of conventional flow cytometry. However, analyzing data from large Ab panels is challenging using traditional biaxial gating strategies. We present, to our knowledge, a novel analysis pipeline to improve analysis of spectral flow cytometry. We employ this method to identify rare T cell populations in aging. We isolated splenocytes from young (2-3 mo old) and aged (18-19 mo old) female C57BL/6N mice and then stained these with a panel of 20 fluorescently labeled Abs. We performed spectral flow cytometry and then data processing and analysis using Python within a Jupyter Notebook environment to perform dimensionality reduction, batch correction, unsupervised clustering, and differential expression analysis. Our analysis of 3,776,804 T cells from 11 spleens revealed 35 distinct T cell clusters identified by surface marker expression. We observed significant differences between young and aged mice, with clusters enriched in one age group over the other. Naive, effector memory, and central memory CD8+ and CD4+ T cell subsets exhibited age-associated changes in abundance and marker expression. We also demonstrate the utility of our pipeline in a human PBMC dataset that used a 50-fluorescent color panel. By leveraging high-dimensional analysis methods, we provide insights into the immune aging process. This approach offers a robust and easily implemented analysis pipeline for spectral flow cytometry data that may facilitate the discovery of novel therapeutic targets for age-related immune dysfunction.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502048","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
Single-cell Sequencing of Circulating Human Plasmablasts during Staphylococcus aureus Bacteremia. 金黄色葡萄球菌菌血症期间循环人体浆细胞的单细胞测序。
IF 3.6 3区 医学
Journal of immunology Pub Date : 2024-10-25 DOI: 10.4049/jimmunol.2300858
Priscilla F Kerkman, Lisanne de Vor, Thomas W van der Vaart, Thijs Ten Doesschate, Remy M Muts, Jamie S Depelteau, Lisette M Scheepmaker, Maartje Ruyken, Carla J C de Haas, Piet C Aerts, Renoud J Marijnissen, Janine Schuurman, Frank J Beurskens, Andrea Gorlani, Bart W Bardoel, Suzan H M Rooijakkers
{"title":"Single-cell Sequencing of Circulating Human Plasmablasts during Staphylococcus aureus Bacteremia.","authors":"Priscilla F Kerkman, Lisanne de Vor, Thomas W van der Vaart, Thijs Ten Doesschate, Remy M Muts, Jamie S Depelteau, Lisette M Scheepmaker, Maartje Ruyken, Carla J C de Haas, Piet C Aerts, Renoud J Marijnissen, Janine Schuurman, Frank J Beurskens, Andrea Gorlani, Bart W Bardoel, Suzan H M Rooijakkers","doi":"10.4049/jimmunol.2300858","DOIUrl":"10.4049/jimmunol.2300858","url":null,"abstract":"<p><p>Staphylococcus aureus is the major cause of healthcare-associated infections, including life-threatening conditions as bacteremia, endocarditis, and implant-associated infections. Despite adequate antibiotic treatment, the mortality of S. aureus bacteremia remains high. This calls for different strategies to treat this infection. In past years, sequencing of Ab repertoires from individuals previously exposed to a pathogen emerged as a successful method to discover novel therapeutic monoclonal Abs and understand circulating B cell diversity during infection. In this paper, we collected peripheral blood from 17 S. aureus bacteremia patients to study circulating plasmablast responses. Using single-cell transcriptome gene expression combined with sequencing of variable heavy and light Ig genes, we retrieved sequences from >400 plasmablasts revealing a high diversity with >300 unique variable heavy and light sequences. More than 200 variable sequences were synthesized to produce recombinant IgGs that were analyzed for binding to S. aureus whole bacterial cells. This revealed four novel monoclonal Abs that could specifically bind to the surface of S. aureus in the absence of Ig-binding surface SpA. Interestingly, three of four mAbs showed cross-reactivity with Staphylococcus epidermidis. Target identification revealed that the S. aureus-specific mAb BC153 targets wall teichoic acid, whereas cross-reactive mAbs BC019, BC020, and BC021 target lipoteichoic acid. All mAbs could induce Fc-dependent phagocytosis of staphylococci by human neutrophils. Altogether, we characterize the active B cell responses to S. aureus in infected patients and identify four functional mAbs against the S. aureus surface, of which three cross-react with S. epidermidis.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502054","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
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