Journal of immunology最新文献_第3页

The Marginal Zone B Cell Compartment and T Cell-independent Antibody Responses Are Supported by B Cell Intrinsic Expression of IRF1. 边缘区 B 细胞区和 T 细胞依赖性抗体反应由 B 细胞内在表达的 IRF1 支持。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-25 DOI: 10.4049/jimmunol.2300575

Jessica N Peel, Eddie-Williams Owiredu, Alexander F Rosenberg, Aaron Silva-Sanchez, Troy D Randall, John F Kearney, Frances E Lund

{"title":"The Marginal Zone B Cell Compartment and T Cell-independent Antibody Responses Are Supported by B Cell Intrinsic Expression of IRF1.","authors":"Jessica N Peel, Eddie-Williams Owiredu, Alexander F Rosenberg, Aaron Silva-Sanchez, Troy D Randall, John F Kearney, Frances E Lund","doi":"10.4049/jimmunol.2300575","DOIUrl":"https://doi.org/10.4049/jimmunol.2300575","url":null,"abstract":"The prototypic IFN-inducible transcription factor, IRF1, not only controls inflammatory gene expression but also regulates T cell and macrophage fate specification and function. Using bone marrow chimeras (80% B6.129S2-Ighmtm1Cgn/J [µMT] + 20% B6.129S2-Irf1tm1Mak/J [Irf1-/-]), we show that IRF1 expression in B cells is required for marginal zone B (MZB) cell development and T cell-independent Ab responses. Although IFNs can induce IRF1 expression in MZB precursors, deletion of the IFN-γR (C57BL/6J [B6], B6.129S7-Ifngr1tm1Agt/J) or IFN-αR (B6[Cg]-Ifnar1tm1Agt/J) did not affect MZB cell development. Instead, BCR and TLR signals promote IRF1 expression and nuclear translocation in MZB cell precursors. In turn, IRF1 is required for Notch2-dependent gene expression in BCR- and TLR-stimulated transitional B cells and development of the MZB cell compartment. Thus, IRF1 regulates MZB-driven T cell-independent Ab responses by regulating Notch programming in MZB precursors and facilitating commitment of these cells to the MZB lineage.","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":"142502056","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

TP53 Codon 72 Polymorphism Impacts Macrophage Activation through Reactive Oxygen Species-Dependent Cell Signaling Alterations. TP53 第 72 号密码子多态性通过活性氧依赖性细胞信号改变影响巨噬细胞活化

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-25 DOI: 10.4049/jimmunol.2400212

Ashok Silwal, Britney Reese, Bhaumik Patel, Yan Li, Martin V Kolev, Ninh M La-Beck, Magdalena M Karbowniczek, Maciej M Markiewski

{"title":"TP53 Codon 72 Polymorphism Impacts Macrophage Activation through Reactive Oxygen Species-Dependent Cell Signaling Alterations.","authors":"Ashok Silwal, Britney Reese, Bhaumik Patel, Yan Li, Martin V Kolev, Ninh M La-Beck, Magdalena M Karbowniczek, Maciej M Markiewski","doi":"10.4049/jimmunol.2400212","DOIUrl":"10.4049/jimmunol.2400212","url":null,"abstract":"The role of the most common TP53 single-nucleotide polymorphism (SNP) at codon 72, which encodes for proline (P72) or arginine (R72), in the regulation of the immune system has not yet been thoroughly explored. We found that this SNP contributes to aggravated inflammatory response in COVID-19 patients resulting from biased macrophage activation. R72-P53 inhibits mitochondrial manganese superoxide dismutase, leading to impaired reactive oxygen species scavenging, oxidation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and, consequently, its inhibition. Reduced PTEN activity causes constitutive activation of the PI3K/Akt pathway, which restricts proinflammatory (M1) and promotes anti-inflammatory (M2) phenotypes through NF-κB and p53 inhibition. In contrast, PTEN-reduced PI3K/Akt activity, in P72 carrying cells, favors M1 phenotypes. LPS-stimulated R72 macrophages fail to reduce tumor growth in a mouse model of cancer, in contrast with P72 macrophages, which preserve M1 phenotype in vivo and reduce tumor growth by enhancing antitumor T cell responses, consistent with antitumor functions of M1 macrophages. In addition, P72 macrophages contributed to increased mortality in a mouse model of LPS-induced endotoxemia. Therefore, given the high frequency of P72 in African Americans, cell signaling alterations driven by codon 72 of TP53 SNP may potentially contribute to differences in clinical outcomes and health disparities in common diseases associated with dysregulated macrophage activation.","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":"142502057","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

CXCL12/CXCR4 Axis Promotes the Chemotaxis and Phagocytosis of B Cells through the PI3K-AKT Signaling Pathway in an Early Vertebrate. CXCL12/CXCR4轴在早期脊椎动物中通过PI3K-AKT信号通路促进B细胞的趋化和吞噬作用

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-23 DOI: 10.4049/jimmunol.2300562

Along Gao, Yuhua Lin, Yiwen Chai, Jugan Han, Liting Wu, Jianmin Ye

{"title":"CXCL12/CXCR4 Axis Promotes the Chemotaxis and Phagocytosis of B Cells through the PI3K-AKT Signaling Pathway in an Early Vertebrate.","authors":"Along Gao, Yuhua Lin, Yiwen Chai, Jugan Han, Liting Wu, Jianmin Ye","doi":"10.4049/jimmunol.2300562","DOIUrl":"https://doi.org/10.4049/jimmunol.2300562","url":null,"abstract":"Chemokines play crucial roles in the regulation of immune cell migration and development. The CXCL12/CXCR4 axis has been extensively studied in mammals, but its regulatory mechanism in teleost fish remains unclear. In this study, we used Nile tilapia (Oreochromis niloticus) as a teleost model to investigate the mediation of the CXCL12/CXCR4 axis in IgM+ B cells. Our findings demonstrate that the CXCL12/CXCR4 axis exhibits chemotactic activity on IgM+ B cells and promotes the phagocytosis of IgM+ B cells. Blocking CXCR4 severely impairs the chemotaxis and phagocytosis of IgM+ B cells in vitro and reduces the percentages and numbers of IgM+ B cells that migrate to peripheral blood after pathogen infection in vivo. This reduction in migration leads to a decrease in the inflammatory response, an increase in tissue bacterial load, and a decrease in survival rate. We also discovered that the evolutionarily conserved PI3K-AKT signaling pathway and Girdin are involved in the immune response during Streptococcus agalactiae infection. Inhibitors of the PI3K-AKT signaling pathway prevent the chemotaxis and phagocytosis of IgM+ B cells, impair the expression and phosphorylation levels of related proteins in vitro, and prevent IgM+ B cells chemotaxis into the peripheral blood after pathogen infection in vivo. Furthermore, CXCR4 blocking significantly downregulates the expression of AKT and Girdin. Overall, our study reveals the regulatory mechanism of the CXCL12/CXCR4 axis on IgM+ B cells via the PI3K-AKT signaling pathway in tilapia, suggesting that the functions of the CXCL12/CXCR4 axis in B cells may be conserved between mammals and teleost fish.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502029","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

Multiplexed Antibody Sequencing and Profiling of the Human Hemagglutinin-specific Memory B Cell Response following Influenza Vaccination. 流感疫苗接种后人类血凝素特异性记忆 B 细胞反应的多重抗体测序和分析。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-23 DOI: 10.4049/jimmunol.2400326

Nagarajan Raju, Kevin J Kramer, Mattia Cavallaro, Roberta A Diotti, Andrea R Shiakolas, Yailin Campos Mota, Robert A Richardson, Ileia J Scheibe, Ted M Ross, Ivelin S Georgiev, Giuseppe A Sautto

{"title":"Multiplexed Antibody Sequencing and Profiling of the Human Hemagglutinin-specific Memory B Cell Response following Influenza Vaccination.","authors":"Nagarajan Raju, Kevin J Kramer, Mattia Cavallaro, Roberta A Diotti, Andrea R Shiakolas, Yailin Campos Mota, Robert A Richardson, Ileia J Scheibe, Ted M Ross, Ivelin S Georgiev, Giuseppe A Sautto","doi":"10.4049/jimmunol.2400326","DOIUrl":"https://doi.org/10.4049/jimmunol.2400326","url":null,"abstract":"Influenza virus is a highly contagious respiratory pathogen causing between 9.4 and 41 million infections per year in the United States in the last decade. Annual vaccination is recommended by the World Health Organization, with the goal to reduce influenza severity and transmission. Ag-specific single B cell sequencing methodologies have opened up new avenues into the dissection of the Ab response to influenza virus. The improvement of these methodologies is pivotal to reduce the associated costs and optimize the operational workflow and throughput, especially in the context of multiple samples. In this study, PBMCs and serum samples were collected longitudinally from eight influenza vaccinees either vaccinated yearly for four consecutive influenza seasons or once for one season. Following the serological and B cell profiling of their polyclonal Ab response to a panel of historical, recent, and next-generation influenza vaccine hemagglutinin (HA) and virus strains, a single multiplexed Ag-specific single B cell sequencing run allowed to capture HA-specific memory B cells that were analyzed for preferential Ig H chain/L chain pairing, isotype/subclass usage, and the presence of public BCR clonotypes across participants. Binding and functional profiles of representative private and public clonotypes confirmed their HA specificity, and their overall binding and functional activity were consistent with those observed at the polyclonal level. Collectively, this high-resolution and multiplexed Ab repertoire analysis demonstrated the validity of this optimized methodology in capturing Ag-specific BCR clonotypes, even in the context of a rare B cell population, such as in the case of the peripheral Ag-specific memory B cells.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502052","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

Homeostatic Macrophages Prevent Preterm Birth and Improve Neonatal Outcomes by Mitigating In Utero Sterile Inflammation in Mice. 稳态巨噬细胞通过减轻小鼠宫内无菌性炎症防止早产并改善新生儿预后

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-21 DOI: 10.4049/jimmunol.2400467

Valeria Garcia-Flores, Zhenjie Liu, Roberto Romero, Roger Pique-Regi, Yi Xu, Derek Miller, Dustyn Levenson, Jose Galaz, Andrew D Winters, Marcelo Farias-Jofre, Jonathan J Panzer, Kevin R Theis, Nardhy Gomez-Lopez

{"title":"Homeostatic Macrophages Prevent Preterm Birth and Improve Neonatal Outcomes by Mitigating In Utero Sterile Inflammation in Mice.","authors":"Valeria Garcia-Flores, Zhenjie Liu, Roberto Romero, Roger Pique-Regi, Yi Xu, Derek Miller, Dustyn Levenson, Jose Galaz, Andrew D Winters, Marcelo Farias-Jofre, Jonathan J Panzer, Kevin R Theis, Nardhy Gomez-Lopez","doi":"10.4049/jimmunol.2400467","DOIUrl":"https://doi.org/10.4049/jimmunol.2400467","url":null,"abstract":"Preterm birth (PTB), often preceded by preterm labor, is a major cause of neonatal morbidity and mortality worldwide. Most PTB cases involve intra-amniotic inflammation without detectable microorganisms, termed in utero sterile inflammation, for which there is no established treatment. In this study, we propose homeostatic macrophages to prevent PTB and adverse neonatal outcomes caused by in utero sterile inflammation. Single-cell atlases of the maternal-fetal interface revealed that homeostatic maternal macrophages are reduced with human labor. M2 macrophage treatment prevented PTB and reduced adverse neonatal outcomes in mice with in utero sterile inflammation. Specifically, M2 macrophages halted premature labor by suppressing inflammatory responses in the amniotic cavity, including inflammasome activation, and mitigated placental and offspring lung inflammation. Moreover, M2 macrophages boosted gut inflammation in neonates and improved their ability to fight systemic bacterial infections. Our findings show that M2 macrophages are a promising strategy to mitigate PTB and improve neonatal outcomes resulting from in utero sterile inflammation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467517","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 Inhibitory Effects of a Factor B-Binding DNA Aptamer Family Supersede the Gain of Function of Factor B Variants Associated with Atypical Hemolytic Uremic Syndrome. 与因子 B 结合的 DNA Aptamer 家族的抑制作用超越了与非典型溶血性尿毒症相关的因子 B 变异的功能增益。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-21 DOI: 10.4049/jimmunol.2400420

Huiquan Duan, Ying Zhang, Matthew R Otis, Daniel W Drolet, Brian V Geisbrecht

{"title":"The Inhibitory Effects of a Factor B-Binding DNA Aptamer Family Supersede the Gain of Function of Factor B Variants Associated with Atypical Hemolytic Uremic Syndrome.","authors":"Huiquan Duan, Ying Zhang, Matthew R Otis, Daniel W Drolet, Brian V Geisbrecht","doi":"10.4049/jimmunol.2400420","DOIUrl":"https://doi.org/10.4049/jimmunol.2400420","url":null,"abstract":"Aptamers are short, single-stranded oligonucleotides that selectively bind to target biomolecules. Although they generally exhibit good binding specificity, their affinities are often limited because of the relative lack of hydrophobic groups in nucleic acids. Chemically modified nucleotides incorporating hydrophobic structures into uracil have been synthesized to address this obstacle. Modified DNA aptamers containing such nonstandard nucleotides have been developed for >20 different complement proteins. These modified aptamers show increased affinity and enhanced serum stability and have potential value as therapeutic agents. We recently conducted a structure/function study on a family of modified DNA aptamers that bind specifically to complement Factor B (FB). This work revealed that these aptamers selectively inhibit the complement alternative pathway (AP) by preventing the formation of the AP complement component C3 (C3) proconvertase complex, C3bB. Certain patients with atypical hemolytic uremic syndrome express gain-of-function variants of FB that enhance the formation of the proconvertase complex and/or decrease the efficacy of endogenous regulators against the C3 convertases they form. To investigate whether these FB-binding aptamers could override the effects of disease-causing mutations in FB, we examined how they interacted with several FB variants, including D279G, F286L, K323E, and K350N, in various assays of complement function. We found that the inhibitory effect of the FB-binding aptamers superseded the gain-of-function mutations in FB, although the aptamers could not dissociate preformed C3 convertases. These findings suggest that FB-binding aptamers could be further developed as a potential treatment for certain atypical hemolytic uremic syndrome patients or those with other diseases characterized by excessive complement activity.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467520","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

Enhancement of Autophagy in Macrophages via the p120-Catenin-Mediated mTOR Signaling Pathway. 通过 p120-Catenin 介导的 mTOR 信号通路增强巨噬细胞的自噬作用

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-18 DOI: 10.4049/jimmunol.2400189

Suganya Kanmani, Xue-Min Song, Paulraj Kanmani, Xiao-Jing Wu, Xiao-Di Tan, Jing Liu, Ji-Ping Wang, Richard D Minshall, Guochang Hu

{"title":"Enhancement of Autophagy in Macrophages via the p120-Catenin-Mediated mTOR Signaling Pathway.","authors":"Suganya Kanmani, Xue-Min Song, Paulraj Kanmani, Xiao-Jing Wu, Xiao-Di Tan, Jing Liu, Ji-Ping Wang, Richard D Minshall, Guochang Hu","doi":"10.4049/jimmunol.2400189","DOIUrl":"https://doi.org/10.4049/jimmunol.2400189","url":null,"abstract":"Autophagy serves as a critical regulator of immune responses in sepsis. Macrophages are vital constituents of both innate and adaptive immunity. In this study, we delved into the intricate role of p120-catenin (p120) in orchestrating autophagy in macrophages in response to endotoxin stimulation. Depletion of p120 effectively suppressed LPS-induced autophagy in both J774A.1 macrophages and murine bone marrow-derived macrophages. LPS not only elevated the interaction between p120 and L chain 3 (LC3) I/II but also facilitated the association of p120 with mammalian target of rapamycin (mTOR). p120 depletion in macrophages by small interfering RNA reduced LPS-induced dissociation of mTOR and Unc-51-like kinase 1 (ULK1), leading to an increase in the phosphorylation of ULK1. p120 depletion also enhanced LPS-triggered macrophage apoptosis, as evidenced by increased levels of cleaved caspase 3, 7-aminoactinomycin D staining, and TUNEL assay. Notably, inhibiting autophagy reversed the decrease in apoptosis caused by LPS stimulation in macrophages overexpressing p120. Additionally, the ablation of p120 inhibited autophagy and accentuated apoptosis in alveolar macrophages in LPS-challenged mice. Collectively, our findings strongly suggest that p120 plays a pivotal role in fostering autophagy while concurrently hindering apoptosis in macrophages, achieved through modulation of the mTOR/ULK1 signaling pathway in sepsis. This underscores the potential of targeting macrophage p120 as an innovative therapeutic avenue for treating inflammatory disorders.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467419","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

Virus-specific Th17 Cells Are Induced by Human Cytomegalovirus after Renal Transplantation. 肾移植后人类巨细胞病毒会诱发病毒特异性 Th17 细胞

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-18 DOI: 10.4049/jimmunol.2300742

Ravi Dhital, Kaitlyn Flint, Irina Kaptsan, Shweta Hegde, Reem Daloul, Masako Shimamura

{"title":"Virus-specific Th17 Cells Are Induced by Human Cytomegalovirus after Renal Transplantation.","authors":"Ravi Dhital, Kaitlyn Flint, Irina Kaptsan, Shweta Hegde, Reem Daloul, Masako Shimamura","doi":"10.4049/jimmunol.2300742","DOIUrl":"10.4049/jimmunol.2300742","url":null,"abstract":"CMV infection and Th17 cells are independently associated with increased risk for late allograft loss after renal transplantation. Although CMV-specific Th17 cells are detectable in animal models and nontransplant clinical populations, evidence linking CMV and Th17 cells after renal transplantation remains unclear. This prospective observational study evaluated a cohort of renal transplant recipients during 12 mo posttransplant to assess the presence of CMV-specific Th17 cells in peripheral blood and their relationship to pretransplant CMV serostatus and CMV DNAemia. CMV-specific Th17 cells were identified among CMV serostatus donor (D)+ and/or recipient (R)+ recipients and expanded during both primary (D+/R-) and reactivated (D+/R+, D-/R+) CMV DNAemia. A subset of CMV-specific Th17 cells coexpressed IFN-γ, indicating a Th1/17 phenotype. These Th17 and Th1/17 cells expressed CCR6, CCR5, activation and terminal differentiation markers (CD95, OX40, HLA-DR, CD57), and a central/effector memory phenotype. CMV-specific Th1/17 cells expressed activating/inhibitory receptors (CD57, 4-1BB, CD160, CTLA-4, PD-1) at higher frequencies than Th17 cells. In contrast, staphylococcal enterotoxin B-induced Th17 cells did not expand during CMV DNAemia, did not differ between CMV serostatus groups over time, expressed CCR6, predominantly coexpressed TNF-α, and had lower expression of activating and inhibitory receptors than pp65-specific Th17 and Th1/17 cells. These data show that CMV-specific Th17 cells expand during episodes of CMV DNAemia among renal transplant recipients, and that these virus-specific Th17 and Th1/17 cells have distinct phenotypes from global circulating Th(1)/17 cells. These results suggest a potential proinflammatory pathway by which CMV-induced Th17 cells may contribute to allograft injury, increasing risk for late allograft loss.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467521","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

Myeloid Cell-Specific Deletion of AMPKα1 Worsens Ocular Bacterial Infection by Skewing Macrophage Phenotypes. 髓系细胞特异性缺失 AMPKα1 会使巨噬细胞表型发生改变，从而加重眼部细菌感染。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-16 DOI: 10.4049/jimmunol.2400282

Sukhvinder Singh, Pawan Kumar Singh, Zeeshan Ahmad, Susmita Das, Marc Foretz, Benoit Viollet, Shailendra Giri, Ashok Kumar

{"title":"Myeloid Cell-Specific Deletion of AMPKα1 Worsens Ocular Bacterial Infection by Skewing Macrophage Phenotypes.","authors":"Sukhvinder Singh, Pawan Kumar Singh, Zeeshan Ahmad, Susmita Das, Marc Foretz, Benoit Viollet, Shailendra Giri, Ashok Kumar","doi":"10.4049/jimmunol.2400282","DOIUrl":"10.4049/jimmunol.2400282","url":null,"abstract":"AMP-activated protein kinase (AMPK) plays a crucial role in governing essential cellular functions such as growth, proliferation, and survival. Previously, we observed increased vulnerability to bacterial (Staphylococcus aureus) endophthalmitis in global AMPKα1 knockout mice. In this study, we investigated the specific involvement of AMPKα1 in myeloid cells using LysMCre;AMPKα1fl mice. Our findings revealed that whereas endophthalmitis resolved in wild-type C57BL/6 mice, the severity of the disease progressively worsened in AMPKα1-deficient mice over time. Moreover, the intraocular bacterial load and inflammatory mediators (e.g., IL-1β, TNF-α, IL-6, and CXCL2) were markedly elevated in the LysMCre;AMPKα1fl mice. Mechanistically, the deletion of AMPKα1 in myeloid cells skewed macrophage polarization toward the inflammatory M1 phenotype and impaired the phagocytic clearance of S. aureus by macrophages. Notably, transferring AMPK-competent bone marrow from wild-type mice to AMPKα1 knockout mice preserved retinal function and mitigated the severity of endophthalmitis. Overall, our study underscores the role of myeloid-specific AMPKα1 in promoting the resolution of inflammation in the eye during bacterial infection. Hence, therapeutic strategies aimed at restoring or enhancing AMPKα1 activity could improve visual outcomes in endophthalmitis and other ocular infections.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467519","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

Alarm Functions of PD-1+ Brain-Resident Memory T Cells. PD-1+ 脑驻留记忆 T 细胞的报警功能

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-10-16 DOI: 10.4049/jimmunol.2400295

Shawn C Musial, Sierra A Kleist, Hanna N Degefu, Myles A Ford, Tiffany Chen, Jordan F Isaacs, Vassiliki A Boussiotis, Alexander G J Skorput, Pamela C Rosato

{"title":"Alarm Functions of PD-1+ Brain-Resident Memory T Cells.","authors":"Shawn C Musial, Sierra A Kleist, Hanna N Degefu, Myles A Ford, Tiffany Chen, Jordan F Isaacs, Vassiliki A Boussiotis, Alexander G J Skorput, Pamela C Rosato","doi":"10.4049/jimmunol.2400295","DOIUrl":"10.4049/jimmunol.2400295","url":null,"abstract":"Resident memory T cells (TRM cells) have been described in barrier tissues as having a \"sensing and alarm\" function where, upon sensing cognate Ag, they alarm the surrounding tissue and orchestrate local recruitment and activation of immune cells. In the immunologically unique and tightly restricted CNS, it remains unclear whether and how brain TRM cells, which express the inhibitory receptor programmed cell death protein 1 (PD-1), alarm the surrounding tissue during Ag re-encounter. Using mouse models, we reveal that TRM cells are sufficient to drive the rapid remodeling of the brain immune landscape through activation of microglia, dendritic cells, NK cells, and B cells, expansion of regulatory T cells, and recruitment of macrophages and monocytic dendritic cells. Moreover, we report that although PD-1 restrained granzyme B upregulation in brain TRM cells reactivated via viral peptide, we observed no apparent effect on cytotoxicity in vivo, or downstream alarm responses within 48 h of TRM reactivation. We conclude that TRM cells are sufficient to trigger rapid immune activation and recruitment in the CNS and may have an unappreciated role in driving neuroinflammation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467418","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