Madison S. Strine, Eric Fagerberg, Patrick W. Darcy, Gabriel M. Barrón, Renata B. Filler, Mia Madel Alfajaro, Nicole D’Angelo-Gavrish, Fang Wang, Vincent R. Graziano, Bridget L. Menasché, Martina Damo, Ya-Ting Wang, Michael R. Howitt, Sanghyun Lee, Nikhil S. Joshi, Daniel Mucida, Craig B. Wilen
{"title":"Intestinal tuft cell immune privilege enables norovirus persistence","authors":"Madison S. Strine, Eric Fagerberg, Patrick W. Darcy, Gabriel M. Barrón, Renata B. Filler, Mia Madel Alfajaro, Nicole D’Angelo-Gavrish, Fang Wang, Vincent R. Graziano, Bridget L. Menasché, Martina Damo, Ya-Ting Wang, Michael R. Howitt, Sanghyun Lee, Nikhil S. Joshi, Daniel Mucida, Craig B. Wilen","doi":"10.1126/sciimmunol.adi7038","DOIUrl":"10.1126/sciimmunol.adi7038","url":null,"abstract":"<div >The persistent murine norovirus strain MNV<sup>CR6</sup> is a model for human norovirus and enteric viral persistence. MNV<sup>CR6</sup> causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although MNV<sup>CR6</sup> induces functional MNV-specific CD8<sup>+</sup> T cells, these lymphocytes fail to clear infection. To examine how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8<sup>+</sup> T cells by adoptively transferring JEDI (just EGFP death inducing) CD8<sup>+</sup> T cells into Gfi1b-GFP tuft cell reporter mice. Unexpectedly, some intestinal tuft cells partially resisted JEDI CD8<sup>+</sup> T cell–mediated killing—unlike Lgr5<sup>+</sup> intestinal stem cells and extraintestinal tuft cells—despite seemingly normal antigen presentation. When targeting intestinal tuft cells, JEDI CD8<sup>+</sup> T cells predominantly adopted a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. JEDI CD8<sup>+</sup> T cells neither cleared nor prevented MNV<sup>CR6</sup> infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen. Ultimately, we show that intestinal tuft cells are relatively resistant to CD8<sup>+</sup> T cells independent of norovirus infection, representing an immune-privileged niche that can be leveraged by enteric microbes.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science ImmunologyPub Date : 2024-03-22DOI: https://www.science.org/doi/10.1126/sciimmunol.adi7038
Madison S. Strine, Eric Fagerberg, Patrick W. Darcy, Gabriel M. Barrón, Renata B. Filler, Mia Madel Alfajaro, Nicole D’Angelo-Gavrish, Fang Wang, Vincent R. Graziano, Bridget L. Menasché, Martina Damo, Ya-Ting Wang, Michael R. Howitt, Sanghyun Lee, Nikhil S. Joshi, Daniel Mucida, Craig B. Wilen
{"title":"Intestinal tuft cell immune privilege enables norovirus persistence","authors":"Madison S. Strine, Eric Fagerberg, Patrick W. Darcy, Gabriel M. Barrón, Renata B. Filler, Mia Madel Alfajaro, Nicole D’Angelo-Gavrish, Fang Wang, Vincent R. Graziano, Bridget L. Menasché, Martina Damo, Ya-Ting Wang, Michael R. Howitt, Sanghyun Lee, Nikhil S. Joshi, Daniel Mucida, Craig B. Wilen","doi":"https://www.science.org/doi/10.1126/sciimmunol.adi7038","DOIUrl":"https://doi.org/https://www.science.org/doi/10.1126/sciimmunol.adi7038","url":null,"abstract":"The persistent murine norovirus strain MNV<sup>CR6</sup> is a model for human norovirus and enteric viral persistence. MNV<sup>CR6</sup> causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although MNV<sup>CR6</sup> induces functional MNV-specific CD8<sup>+</sup> T cells, these lymphocytes fail to clear infection. To examine how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8<sup>+</sup> T cells by adoptively transferring JEDI (just EGFP death inducing) CD8<sup>+</sup> T cells into Gfi1b-GFP tuft cell reporter mice. Unexpectedly, some intestinal tuft cells partially resisted JEDI CD8<sup>+</sup> T cell–mediated killing—unlike Lgr5<sup>+</sup> intestinal stem cells and extraintestinal tuft cells—despite seemingly normal antigen presentation. When targeting intestinal tuft cells, JEDI CD8<sup>+</sup> T cells predominantly adopted a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. JEDI CD8<sup>+</sup> T cells neither cleared nor prevented MNV<sup>CR6</sup> infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen. Ultimately, we show that intestinal tuft cells are relatively resistant to CD8<sup>+</sup> T cells independent of norovirus infection, representing an immune-privileged niche that can be leveraged by enteric microbes.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140192599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science ImmunologyPub Date : 2024-03-22DOI: https://www.science.org/doi/10.1126/sciimmunol.adi8150
Theo van den Broek, Kristine Oleinika, Siti Rahmayanti, Carlos Castrillon, Cees E. van der Poel, Michael C. Carroll
{"title":"Invasion of spontaneous germinal centers by naive B cells is rapid and persistent","authors":"Theo van den Broek, Kristine Oleinika, Siti Rahmayanti, Carlos Castrillon, Cees E. van der Poel, Michael C. Carroll","doi":"https://www.science.org/doi/10.1126/sciimmunol.adi8150","DOIUrl":"https://doi.org/https://www.science.org/doi/10.1126/sciimmunol.adi8150","url":null,"abstract":"In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions to limit autoimmune pathologies, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs by wild-type B cells required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a tool for identifying early events in the breaking of B cell tolerance in autoimmunity.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140196086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivan Kosik, Jefferson Da Silva Santos, Mathew Angel, Zhe Hu, Jaroslav Holly, James S. Gibbs, Tanner Gill, Martina Kosikova, Tiansheng Li, William Bakhache, Patrick T. Dolan, Hang Xie, Sarah F. Andrews, Rebecca A. Gillespie, Masaru Kanekiyo, Adrian B. McDermott, Theodore C. Pierson, Jonathan W. Yewdell
{"title":"C1q enables influenza hemagglutinin stem binding antibodies to block viral attachment and broadens the antibody escape repertoire","authors":"Ivan Kosik, Jefferson Da Silva Santos, Mathew Angel, Zhe Hu, Jaroslav Holly, James S. Gibbs, Tanner Gill, Martina Kosikova, Tiansheng Li, William Bakhache, Patrick T. Dolan, Hang Xie, Sarah F. Andrews, Rebecca A. Gillespie, Masaru Kanekiyo, Adrian B. McDermott, Theodore C. Pierson, Jonathan W. Yewdell","doi":"10.1126/sciimmunol.adj9534","DOIUrl":"10.1126/sciimmunol.adj9534","url":null,"abstract":"<div >Antigenic drift, the gradual accumulation of amino acid substitutions in the influenza virus hemagglutinin (HA) receptor protein, enables viral immune evasion. Antibodies (Abs) specific for the drift-resistant HA stem region are a promising universal influenza vaccine target. Although anti-stem Abs are not believed to block viral attachment, here we show that complement component 1q (C1q), a 460-kilodalton protein with six Ab Fc-binding domains, confers attachment inhibition to anti-stem Abs and enhances their fusion and neuraminidase inhibition. As a result, virus neutralization activity in vitro is boosted up to 30-fold, and in vivo protection from influenza PR8 infection in mice is enhanced. These effects reflect increased steric hindrance and not increased Ab avidity. C1q greatly expands the anti-stem Ab viral escape repertoire to include residues throughout the HA, some of which cause antigenic alterations in the globular region or modulate HA receptor avidity. We also show that C1q enhances the neutralization activity of non–receptor binding domain anti–SARS-CoV-2 spike Abs, an effect dependent on spike density on the virion surface. These findings demonstrate that C1q can greatly expand Ab function and thereby contribute to viral evolution and immune escape.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Theo van den Broek, Kristine Oleinika, Siti Rahmayanti, Carlos Castrillon, Cees E. van der Poel, Michael C. Carroll
{"title":"Invasion of spontaneous germinal centers by naive B cells is rapid and persistent","authors":"Theo van den Broek, Kristine Oleinika, Siti Rahmayanti, Carlos Castrillon, Cees E. van der Poel, Michael C. Carroll","doi":"10.1126/sciimmunol.adi8150","DOIUrl":"10.1126/sciimmunol.adi8150","url":null,"abstract":"<div >In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions to limit autoimmune pathologies, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs by wild-type B cells required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a tool for identifying early events in the breaking of B cell tolerance in autoimmunity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katherine Z. Sanidad, Stephanie L. Rager, Hannah C. Carrow, Aparna Ananthanarayanan, Ryann Callaghan, Lucy R. Hart, Tingting Li, Purnima Ravisankar, Julia A. Brown, Mohammed Amir, Jenny C. Jin, Alexandria Rose Savage, Ryan Luo, Florencia Mardorsky Rowdo, M. Laura Martin, Randi B. Silver, Chun-Jun Guo, Jan Krumsiek, Naohiro Inohara, Melody Y. Zeng
{"title":"Gut bacteria–derived serotonin promotes immune tolerance in early life","authors":"Katherine Z. Sanidad, Stephanie L. Rager, Hannah C. Carrow, Aparna Ananthanarayanan, Ryann Callaghan, Lucy R. Hart, Tingting Li, Purnima Ravisankar, Julia A. Brown, Mohammed Amir, Jenny C. Jin, Alexandria Rose Savage, Ryan Luo, Florencia Mardorsky Rowdo, M. Laura Martin, Randi B. Silver, Chun-Jun Guo, Jan Krumsiek, Naohiro Inohara, Melody Y. Zeng","doi":"10.1126/sciimmunol.adj4775","DOIUrl":"10.1126/sciimmunol.adj4775","url":null,"abstract":"<div >The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown. We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice resulted in long-term T cell–mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adj4775","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science ImmunologyPub Date : 2024-03-15DOI: https://www.science.org/doi/10.1126/sciimmunol.adn4958
Veera Panova, Arianne C. Richard
{"title":"A metabolic pacer ensures smooth running of the lymphocyte activation race","authors":"Veera Panova, Arianne C. Richard","doi":"https://www.science.org/doi/10.1126/sciimmunol.adn4958","DOIUrl":"https://doi.org/https://www.science.org/doi/10.1126/sciimmunol.adn4958","url":null,"abstract":"Upon lymphocyte stimulation, accumulation of intracellular NAD(H) reflects the strength of antigen receptor signals and controls the rate of cell cycle entry and proliferation (see related Research Article by Turner <i>et al</i>.).","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Science ImmunologyPub Date : 2024-03-15DOI: https://www.science.org/doi/10.1126/sciimmunol.adh5318
Abani Kanta Naik, Danielle J. Dauphars, Elizabeth Corbett, Lunden Simpson, David G. Schatz, Michael S. Krangel
{"title":"RORγt up-regulates RAG gene expression in DP thymocytes to expand the Tcra repertoire","authors":"Abani Kanta Naik, Danielle J. Dauphars, Elizabeth Corbett, Lunden Simpson, David G. Schatz, Michael S. Krangel","doi":"https://www.science.org/doi/10.1126/sciimmunol.adh5318","DOIUrl":"https://doi.org/https://www.science.org/doi/10.1126/sciimmunol.adh5318","url":null,"abstract":"Recombination activating gene (RAG) expression increases as thymocytes transition from the CD4<sup>−</sup>CD8<sup>−</sup> double-negative (DN) to the CD4<sup>+</sup>CD8<sup>+</sup> double-positive (DP) stage, but the physiological importance and mechanism of transcriptional up-regulation are unknown. Here, we show that a DP-specific component of the recombination activating genes antisilencer (DPASE) provokes elevated RAG expression in DP thymocytes. Mouse DP thymocytes lacking the DPASE display RAG expression equivalent to that in DN thymocytes, but this supports only a partial <i>Tcra</i> repertoire due to inefficient secondary Vα-Jα rearrangement. These data indicate that RAG up-regulation is required for a replete <i>Tcra</i> repertoire and that RAG expression is fine-tuned during lymphocyte development to meet the requirements of distinct antigen receptor loci. We further show that transcription factor RORγt directs RAG up-regulation in DP thymocytes by binding to the DPASE and that RORγt influences the <i>Tcra</i> repertoire by binding to the <i>Tcra</i> enhancer. These data, together with prior work showing RORγt to control <i>Tcra</i> rearrangement by regulating DP thymocyte proliferation and survival, reveal RORγt to orchestrate multiple pathways that support formation of the <i>Tcra</i> repertoire.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140161955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucien Turner, Tran Ngoc Van Le, Eric Cross, Clemence Queriault, Montana Knight, Krittin Trihemasava, James Davis, Patrick Schaefer, Janet Nguyen, Jimmy Xu, Brian Goldspiel, Elise Hall, Kelly Rome, Michael Scaglione, Joel Eggert, Byron Au-Yeung, Douglas C. Wallace, Clementina Mesaros, Joseph A. Baur, Will Bailis
{"title":"Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics","authors":"Lucien Turner, Tran Ngoc Van Le, Eric Cross, Clemence Queriault, Montana Knight, Krittin Trihemasava, James Davis, Patrick Schaefer, Janet Nguyen, Jimmy Xu, Brian Goldspiel, Elise Hall, Kelly Rome, Michael Scaglione, Joel Eggert, Byron Au-Yeung, Douglas C. Wallace, Clementina Mesaros, Joseph A. Baur, Will Bailis","doi":"10.1126/sciimmunol.adj7238","DOIUrl":"10.1126/sciimmunol.adj7238","url":null,"abstract":"<div >Adaptive immunity requires the expansion of high-affinity lymphocytes from a heterogeneous pool. Whereas current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Here, we identify nicotinamide adenine dinucleotide (NAD) biosynthesis as a biochemical hub for the T cell receptor affinity–dependent metabolome. Through this central anabolic role, we found that NAD biosynthesis governs a quiescence exit checkpoint, thereby pacing proliferation. Normalizing cellular NAD(H) likewise normalizes proliferation across affinities, and enhancing NAD biosynthesis permits the expansion of lower affinity clones. Furthermore, single-cell differences in NAD(H) could predict division potential for both T and B cells, before the first division, unmixing proliferative heterogeneity. We believe that this supports a broader paradigm in which complex signaling networks converge on metabolic pathways to control single-cell behavior.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adj7238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A metabolic pacer ensures smooth running of the lymphocyte activation race","authors":"Veera Panova, Arianne C. Richard","doi":"10.1126/sciimmunol.adn4958","DOIUrl":"10.1126/sciimmunol.adn4958","url":null,"abstract":"<div >Upon lymphocyte stimulation, accumulation of intracellular NAD(H) reflects the strength of antigen receptor signals and controls the rate of cell cycle entry and proliferation (see related Research Article by Turner <i>et al</i>.).</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adn4958","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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