Cell reportsPub Date : 2026-09-29DOI: 10.1016/j.celrep.2026.118043
Klil Cohen Yaron, Yaakov Socol, Noam Yedidi, Michal Bejerano-Sagie, Miriam Ravins, Shira Fine-Leebhoff, Liron Birimberg-Schwartz, Myriam Grunewald, Karthik Hullahalli, Afonso de Sousa Vieira, Matthew K Waldor, Sina Bartfeld, Sigal Ben-Yehuda, Ilan Rosenshine
{"title":"Dual roles of host N-glycosylation in enteropathogenic Escherichia coli infection.","authors":"Klil Cohen Yaron, Yaakov Socol, Noam Yedidi, Michal Bejerano-Sagie, Miriam Ravins, Shira Fine-Leebhoff, Liron Birimberg-Schwartz, Myriam Grunewald, Karthik Hullahalli, Afonso de Sousa Vieira, Matthew K Waldor, Sina Bartfeld, Sigal Ben-Yehuda, Ilan Rosenshine","doi":"10.1016/j.celrep.2026.118043","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118043","url":null,"abstract":"<p><p>Host factors determine pathogen tropism but knowledge of host genes facilitating enteropathogenic Escherichia coli (EPEC) infection is limited. To identify host determinants required for infection by EPEC, we performed two independent genome-scale CRISPR-Cas9 screens. Both converged on host N-glycosylation as a critical requirement for infection. Genetic or pharmacological inhibition of N-glycan maturation revealed that N-glycosylation promotes infection through two distinct pathways. First, N-linked poly-N-acetyllactosamine glycans serve as receptors for the major EPEC adhesin, the bundle-forming pilus (BFP). Second, perturbation of N-glycosylation compromises host membrane structure, resulting in reduced type III secretion system activity, independently of host cell attachment. Using epithelial monolayers derived from human colon and jejunum organoids, we further show that EPEC attachment inversely correlates with terminal mannose exposure, suggesting glycan composition may be involved in determining intestinal tropism. Together, these findings establish host N-glycan maturation as a key host pathway exploited during enteric infection.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118043"},"PeriodicalIF":7.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell reportsPub Date : 2026-09-29DOI: 10.1016/j.celrep.2026.118070
Victoria P Schuster, Naomi Berkowitz, Kasidy Brown, Catherine Rousculp, Valentina Laverde, Julia R Unsworth, Megan K Ruhland
{"title":"Contextual control of CD8<sup>+</sup> T cell priming by dendritic cell subsets in tumor and inflammatory microenvironments.","authors":"Victoria P Schuster, Naomi Berkowitz, Kasidy Brown, Catherine Rousculp, Valentina Laverde, Julia R Unsworth, Megan K Ruhland","doi":"10.1016/j.celrep.2026.118070","DOIUrl":"10.1016/j.celrep.2026.118070","url":null,"abstract":"<p><p>Migratory and lymph node-resident dendritic cells occupy distinct niches and drive T cell activation during infection, vaccination, and cancer. How tissue context and dendritic cell subset-specific transcriptional programs integrate to shape CD8<sup>+</sup> T cell priming remains incompletely defined. Using fluorescent antigen, we track antigen distribution, dendritic cell transcriptional programming, and cross-presentation across tumor, inflamed, and steady-state tissues. Tumor antigen is more widely distributed among lymph node dendritic cells than skin-derived antigen. Migratory type 1 dendritic cells display higher expression of cross-presentation machinery and superior per-cell cross-presentation and induction of CD8<sup>+</sup> T cell proliferation compared to lymph node-resident type 1 dendritic cells. Ultimately, antigen access and cell-specific cross-presentation efficiency together predict the quality of CD8<sup>+</sup> T cell priming. These results identify migratory type 1 dendritic cells as central mediators of antitumor CD8<sup>+</sup> T cell responses and support therapeutic strategies that augment the efficiency of resident dendritic cell cross-presentation.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118070"},"PeriodicalIF":7.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell reportsPub Date : 2026-09-29DOI: 10.1016/j.celrep.2026.117981
Barbara Puzek, Paul R Wratil, Christian Janke, Thu Giang Le Thi, Raquel Rubio-Acero, Gaia Lupoli, Irene Charlotte Schoof, Marcel Stern, Ana Zhelyazkova, Jochen Rech, Alexander Choukér, Berthold Koletzko, Andreas Wieser, Helga P Török, Noemi Castelletti, Oliver T Keppler, Christof Geldmacher, Veit Hornung, Eleftheria Zeggini, Kristina Adorjan, Michael Hoelscher, Sibylle Koletzko, Sarah Kim-Hellmuth
{"title":"Genetic variation in HLA, IGKV, and HHEX loci influences mRNA vaccine-induced humoral protection against COVID-19.","authors":"Barbara Puzek, Paul R Wratil, Christian Janke, Thu Giang Le Thi, Raquel Rubio-Acero, Gaia Lupoli, Irene Charlotte Schoof, Marcel Stern, Ana Zhelyazkova, Jochen Rech, Alexander Choukér, Berthold Koletzko, Andreas Wieser, Helga P Török, Noemi Castelletti, Oliver T Keppler, Christof Geldmacher, Veit Hornung, Eleftheria Zeggini, Kristina Adorjan, Michael Hoelscher, Sibylle Koletzko, Sarah Kim-Hellmuth","doi":"10.1016/j.celrep.2026.117981","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.117981","url":null,"abstract":"<p><p>Humoral immune responses to COVID-19 vaccination vary widely across individuals, yet the genetic determinants of functional antibody protection beyond binding antibodies after two immunizations remain poorly understood. We performed genome-wide association studies on antigen-specific antibody concentrations and live-virus neutralization activities after two and three vaccine doses in two German cohorts of SARS-CoV-2 infection-naïve individuals (RisCoin study n = 2,877; KoCo19 study n = 1,654). We found the HLA locus to be associated with differential live-virus neutralizing and anti-SARS-CoV-2 spike antibodies after both the second and third vaccinations. Consistent with its effect on third-dose neutralization, the HLA was additionally associated with a reduced incidence of breakthrough infection. We further replicated an association with antibody concentrations at the IGKV locus and discovered an association at the HHEX locus, implicating pathways linked to memory B-cell biology. Together, these findings reveal host genetic factors shaping neutralizing immunity and vaccine-induced protection against infection, with implications for personalized vaccination strategies.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"117981"},"PeriodicalIF":7.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell reportsPub Date : 2026-09-28DOI: 10.1016/j.celrep.2026.118127
Madhuja Samaddar, Gabriel A Fitzgerald, Ann Hong Nguyen, Sonnet S Davis, Shourya Jain, Jian Guo, Nicholas E Propson, Bettina van Lengerich, Yajuan Shi, Srijana Balasundar, Lionel Rougé, Jamal Alkabsh, Anil Rana, Julie Yi, Marcus Y Chin, Isabel A Becerra, Annie Arguello, Brian M Fox, Todd Logan, Jung H Suh, Anastasia G Henry, Gilbert Di Paolo
{"title":"Retraction Notice to: Lysosomal polyamine storage upon ATP13A2 loss impairs β-glucocerebrosidase via altered lysosomal pH and electrostatic hydrolase-lipid interactions.","authors":"Madhuja Samaddar, Gabriel A Fitzgerald, Ann Hong Nguyen, Sonnet S Davis, Shourya Jain, Jian Guo, Nicholas E Propson, Bettina van Lengerich, Yajuan Shi, Srijana Balasundar, Lionel Rougé, Jamal Alkabsh, Anil Rana, Julie Yi, Marcus Y Chin, Isabel A Becerra, Annie Arguello, Brian M Fox, Todd Logan, Jung H Suh, Anastasia G Henry, Gilbert Di Paolo","doi":"10.1016/j.celrep.2026.118127","DOIUrl":"10.1016/j.celrep.2026.118127","url":null,"abstract":"","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118127"},"PeriodicalIF":7.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell reportsPub Date : 2026-09-26DOI: 10.1016/j.celrep.2026.118072
Ge-Xin Zhao, Peng-Lin Li, Bo-Yu Yuan, Qing-Hua Luo, Ting Li, Hai-Yun Ma, Rui-Juan Huang, Guo-Long Bu, Chu Xie, Pei-Huang Wu, Hang Zhou, Wen-Ting Du, Jing Wang, Da-Jun Fang, Mu-Sheng Zeng, Hao-Hao Dong, Guo-Kai Feng, Qian Zhong, Cong Sun
{"title":"Epstein-Barr virus gp350 neutralizing epitopes define distinct sites of vulnerability.","authors":"Ge-Xin Zhao, Peng-Lin Li, Bo-Yu Yuan, Qing-Hua Luo, Ting Li, Hai-Yun Ma, Rui-Juan Huang, Guo-Long Bu, Chu Xie, Pei-Huang Wu, Hang Zhou, Wen-Ting Du, Jing Wang, Da-Jun Fang, Mu-Sheng Zeng, Hao-Hao Dong, Guo-Kai Feng, Qian Zhong, Cong Sun","doi":"10.1016/j.celrep.2026.118072","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118072","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is a widespread human herpesvirus linked to several malignancies, yet no vaccine has been approved. Its major surface glycoprotein, gp350, mediates attachment to B cells via CR2 binding, but gp350-based vaccines have shown limited protection, raising questions about its neutralizing epitopes and mechanisms. Here, we isolated human monoclonal antibodies from a phage-display library derived from EBV-seropositive donors. Several antibodies showed potent neutralization, including 1A12, which conferred robust protection in a humanized mouse model by markedly reducing viral load and disease pathology. Epitope mapping and structural analysis revealed three distinct antigenic clusters on gp350, including a neutralizing epitope in the distal D3 domain recognized by 1H5, which neutralizes EBV via a post-attachment mechanism. These findings define vulnerable sites on gp350 and offer structural and mechanistic insights for developing next-generation EBV vaccines and antibody-based therapies.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118072"},"PeriodicalIF":7.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antigen-specific regulatory T cells eliminate cognate CD4 effector T cells through perforin, granzyme B, and Bim.","authors":"Yanyu Ye, Haoyue Zheng, Jiaqi Duan, Lihua Mo, Yun Liao, Yadong Zheng, Liguo Li, Pengyuan Zheng, Haiyang Han, Chenyang Li, Xiaoyu Liu, Pingchang Yang","doi":"10.1016/j.celrep.2026.118074","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118074","url":null,"abstract":"<p><p>T cells (Tregs) maintain immune tolerance, yet how they selectively eliminate cognate CD4<sup>+</sup> effector T cells remains unclear. We propose a co-activation-dependent elimination mechanism, conceptually akin to synthetic lethality. Using in vitro co-cultures, we show that simultaneous peptide-MHC II recognition by Tregs and responders is required to trigger apoptosis-a \"double-lock\" condition. Dual activation induces perforin and granzyme B in Tregs, while responders become susceptible via TCR-driven Bim upregulation. Conditional deletion of Gzmb, Prf1, or Bcl2l11 abrogates killing. In an OVA-driven airway inflammation model, wild-type but not granzyme B-deficient Tregs reduce lung effector T cells and inflammation, with increased cleaved caspase-3 in targets. This effect requires cognate antigen and occurs without Treg conversion. Human assays recapitulate these findings. Our work defines stringent molecular requirements for Treg-mediated cytotoxicity, informing therapeutic strategies for allergy, autoimmunity, and cancer.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118074"},"PeriodicalIF":7.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Activation of TREM2 via single-domain antibodies improves synaptic and cognitive function in 5×FAD mice.","authors":"Xiaoxiao Yu, Qiaoyun Ren, Yanchun Gao, Sha Xie, Rui Dang, Jinguo Meng, Zhipeng Su, Meng Li, Yuanbo Ao, An Liu, Yanan Wang, Wei Xie","doi":"10.1016/j.celrep.2026.118063","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118063","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, and dysfunction of triggering receptor expressed on myeloid cells 2 (TREM2) in microglia increases AD risk. TREM2 activation promotes protective microglial functions and mitigates AD pathology. Although TREM2-activating antibodies show therapeutic potential, the mechanisms underlying TREM2-mediated rescue effects remain unclear. Here, we show that two TREM2-activating single-domain antibodies (sdAbs), 10C11 and 10E12, activate microglia and rescue cognitive deficits in early-stage transgenic mice with five familial Alzheimer's disease mutations (5×FAD) following ventral hippocampal injection. 10E12 reduces Aβ plaques and preserves synaptic function, whereas 10C11 protects synapses without affecting plaque burden. Both antibodies reduce C1q levels in AD model mice, suggesting that TREM2 activation exerts multifaceted functions in AD. Together, this study presents two TREM2-targeting sdAbs with AD therapeutic potential and provides insights into the cellular mechanisms underlying TREM2 activation and microglial modulation.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118063"},"PeriodicalIF":7.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell reportsPub Date : 2026-09-26DOI: 10.1016/j.celrep.2026.118058
Eve K Brown, Cora Stegmann, Hannah Biermann, Verena Pittl, Mara Duven, Anja C M de Bruin, Elena Neumann, Gisa Gerold
{"title":"Chikungunya virus uses the tetraspanins CD63, CD9, and CD151 to replicate in human synovial fibroblasts.","authors":"Eve K Brown, Cora Stegmann, Hannah Biermann, Verena Pittl, Mara Duven, Anja C M de Bruin, Elena Neumann, Gisa Gerold","doi":"10.1016/j.celrep.2026.118058","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118058","url":null,"abstract":"<p><p>The arthritogenic alphavirus chikungunya virus (CHIKV) causes debilitating long-lasting joint pain. Host factors used by CHIKV to infect joint cells are largely unknown. Here, we evaluated the role of the 19 tetraspanins expressed in primary human synovial fibroblasts in virus infection. The exosome-associated tetraspanins CD63, CD9, and CD151 supported CHIKV infection of joint fibroblasts. Silencing of CD63 and CD151 reduced subgenomic replicon activity. CD9 localized in close proximity to replication sites and its silencing reduced intracellular CHIKV genome accumulation. Silencing of all three tetraspanins reduced progeny virus production. While these tetraspanins were dispensable for CHIKV entry into joint fibroblasts, the receptor MXRA8 promoted cell entry. Our findings demonstrate that CHIKV exploits tetraspanins as host factors in synovial fibroblasts, shedding light on molecular mechanisms underlying CHIKV pathogenesis in joint tissues.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118058"},"PeriodicalIF":7.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell reportsPub Date : 2026-09-26DOI: 10.1016/j.celrep.2026.118020
Jae-I Moon, Seung Gwa Park, Heein Yoon, Wenyue Yu, Dongkyu Lee, Sehwan Ahn, Young-Dan Cho, Kyung Mi Woo, Andre J van Wijnen, Ki-Tae Kim, Woo-Jin Kim, Hyun-Mo Ryoo
{"title":"Nucleome dynamics and histone priming by pioneer transcription factors drive osteoblast differentiation.","authors":"Jae-I Moon, Seung Gwa Park, Heein Yoon, Wenyue Yu, Dongkyu Lee, Sehwan Ahn, Young-Dan Cho, Kyung Mi Woo, Andre J van Wijnen, Ki-Tae Kim, Woo-Jin Kim, Hyun-Mo Ryoo","doi":"10.1016/j.celrep.2026.118020","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118020","url":null,"abstract":"<p><p>Functional maturation of osteoblasts from skeletal stem cells requires genome-wide transcriptional reprogramming, coincident with remodeling of transcribed (A) and inactive (B) chromatin compartments. Here, we assessed whether pioneer factor-driven histone activation links compartment remodeling to osteogenic transcriptional control. Integrative high-throughput 3D genome profiling analyses revealed that early reprogramming is governed by higher-order 3D genome regulation tightly coupled to A/B remodeling near osteogenic loci. Notably, B-to-A shifts were pre-marked in pre-osteoblasts by active histone modifications, indicative of histone priming, which was followed by gene activation upon osteogenic induction. Mechanistically, we identify ETS1 as a pioneer factor that recruits p300 (EP300) to establish histone activation-mediated priming and drive A-compartment shifts. This stage-specific regulation is evident in both cultured osteoblasts and during embryonic calvarial development in vivo. Our findings establish that pioneer factor-mediated histone priming contributes to global 3D genome reorganization to drive osteogenesis.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118020"},"PeriodicalIF":7.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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