Nature Immunology最新文献

{"title":"Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption","authors":"Susan Pereira Ribeiro, Zachary Strongin, Hugo Soudeyns, Felipe ten-Caten, Khader Ghneim, Gabriela Pacheco Sanchez, Giuliana Xavier de Medeiros, Perla Mariana Del Rio Estrada, Adam-Nicolas Pelletier, Timothy Hoang, Kevin Nguyen, Justin Harper, Sherrie Jean, Chelsea Wallace, Robert Balderas, Jeffrey D. Lifson, Gopalan Raghunathan, Eric Rimmer, Cinthia Pastuskova, Guoxin Wu, Luca Micci, Ruy M. Ribeiro, Chi Ngai Chan, Jacob D. Estes, Guido Silvestri, Daniel M. Gorman, Bonnie J. Howell, Daria J. Hazuda, Mirko Paiardini, Rafick P. Sekaly","doi":"10.1038/s41590-024-01952-4","DOIUrl":"10.1038/s41590-024-01952-4","url":null,"abstract":"Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac239-infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8+ T cells in lymph nodes and reduced expression of BCL-2 in CD4+ T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4+ and CD8+ T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART. When monkeys are infected with a virus similar to HIV, treated with antiretroviral therapy (ART), and are administered a ‘combo therapy’ made of antibodies against molecules that inhibit immune responses, they control viral rebound when ART is discontinued for more than 6 months","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01952-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170884","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":"An IGHG1 variant exhibits polarized prevalence and confers enhanced IgG1 antibody responses against life-threatening organisms","authors":"Wenbo Sun, Tingyu Yang, Fengming Sun, Panhong Liu, Ji Gao, Xianmei Lan, Wei Xu, Yuhong Pang, Tong Li, Cuifeng Li, Qingtai Liang, Haoze Chen, Xiaohang Liu, Wenting Tan, Huanhuan Zhu, Fang Wang, Fanjun Cheng, Weiwei Zhai, Han-Na Kim, Jingren Zhang, Linqi Zhang, Lu Lu, Qiaoran Xi, Guohong Deng, Yanyi Huang, Xin Jin, Xiangjun Chen, Wanli Liu","doi":"10.1038/s41590-024-01944-4","DOIUrl":"10.1038/s41590-024-01944-4","url":null,"abstract":"Evolutionary pressures sculpt population genetics, whereas immune adaptation fortifies humans against life-threatening organisms. How the evolution of selective genetic variation in adaptive immune receptors orchestrates the adaptation of human populations to contextual perturbations remains elusive. Here, we show that the G396R coding variant within the human immunoglobulin G1 (IgG1) heavy chain presents a concentrated prevalence in Southeast Asian populations. We uncovered a 190-kb genomic linkage disequilibrium block peaked in close proximity to this variant, suggestive of potential Darwinian selection. This variant confers heightened immune resilience against various pathogens and viper toxins in mice. Mechanistic studies involving severe acute respiratory syndrome coronavirus 2 infection and vaccinated individuals reveal that this variant enhances pathogen-specific IgG1+ memory B cell activation and antibody production. This G396R variant may have arisen on a Neanderthal haplotype background. These findings underscore the importance of an IGHG1 variant in reinforcing IgG1 antibody responses against life-threatening organisms, unraveling the intricate interplay between human evolution and immune adaptation. Liu and colleagues show that a previously described G396R variant of the human IGHG1 gene offers increased protection from SARS-CoV-2 and bacterial infections.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166301","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}

{"title":"Author Correction: Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus","authors":"Mahmoud Al-Azab, Elina Idiiatullina, Ziyang Liu, Meng Lin, Katja Hrovat-Schaale, Huifang Xian, Jianheng Zhu, Mandy Yang, Bingtai Lu, Zhiyao Zhao, Yiyi Liu, Jingjie Chang, Xiaotian Li, Caiqin Guo, Yunfeng Liu, Qi Wu, Jiazhang Chen, Chaoting Lan, Ping Zeng, Jun Cui, Xia Gao, Wenhao Zhou, Yan Zhang, Yuxia Zhang, Seth L. Masters","doi":"10.1038/s41590-024-01969-9","DOIUrl":"10.1038/s41590-024-01969-9","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01969-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291761","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":"CD45 threads the needle of cytokine cancer immunotherapy","authors":"Nils Wellhausen, Saar Gill","doi":"10.1038/s41590-024-01956-0","DOIUrl":"10.1038/s41590-024-01956-0","url":null,"abstract":"Immunocytokines are cytokine-based fusion proteins with therapeutic potential. New CD45-targeted immunocytokines can reprogram systemic anti-tumor immunity by prolonged retention on T cells and dendritic cells while minimizing systemic toxicities through intratumoral delivery.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158754","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}

{"title":"A pinch of salt boosts T cell function","authors":"Karina L. Hajdu, Lorène Rousseau, Ping-Chih Ho","doi":"10.1038/s41590-024-01946-2","DOIUrl":"10.1038/s41590-024-01946-2","url":null,"abstract":"Effector CD8+ T cells with cytotoxic ability are crucial for immunotherapy success. Two studies show that salt (NaCl) supplementation can enhance the effector function of CD8+ T cells and boost their antitumor responses.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158753","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}

{"title":"The promise and reality of new immune profiling technologies","authors":"Sara Suliman, David P. Maison, Timothy J. Henrich","doi":"10.1038/s41590-024-01948-0","DOIUrl":"10.1038/s41590-024-01948-0","url":null,"abstract":"This Comment discusses the explosion in innovative systems biology approaches in infectious disease studies. We outline the numerous challenges associated with these technologies from standardizing data science approaches to reproducibility of findings, as well as cost.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142438","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}

{"title":"Emerging tumor repression of immune recognition is reversed by inhibiting DNA methylation","authors":"","doi":"10.1038/s41590-024-01947-1","DOIUrl":"10.1038/s41590-024-01947-1","url":null,"abstract":"Tumor cells in emerging cancers modify their gene expression to avoid immune control, a process known as immunoediting. We found that genome-wide gene expression changes in breast tumors after oncogene induction in genetically engineered mice were dominated by the epigenetic repression of innate and adaptive immune genes. Immunoevasion by tumors was reversed by a DNA methyltransferase inhibitor.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138030","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}

{"title":"γδ T cells tune allergic itch","authors":"Laurie A. Dempsey","doi":"10.1038/s41590-024-01954-2","DOIUrl":"10.1038/s41590-024-01954-2","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133265","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}

{"title":"The delivery device of SARS-CoV-2 mucosal vaccine matters","authors":"Fanchong Jian, Yunlong Cao","doi":"10.1038/s41590-024-01950-6","DOIUrl":"10.1038/s41590-024-01950-6","url":null,"abstract":"Mucosal vaccine boosters are expected to enhance protection against SARS-CoV-2 infection. A study now reveals that the delivery device — through either intranasal sprayers or nebulizers — also influences the mucosal immunity and protection efficacy in non-human primates.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123707","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}

{"title":"Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates","authors":"Matthew Gagne, Barbara J. Flynn, Shayne F. Andrew, Josue Marquez, Dillon R. Flebbe, Anna Mychalowych, Evan Lamb, Meredith E. Davis-Gardner, Matthew R. Burnett, Leonid A. Serebryannyy, Bob C. Lin, Zohar E. Ziff, Erin Maule, Robin Carroll, Mursal Naisan, Yogita Jethmalani, Laurent Pessaint, John-Paul M. Todd, Nicole A. Doria-Rose, James Brett Case, Igor P. Dmitriev, Elena A. Kashentseva, Baoling Ying, Alan Dodson, Katelyn Kouneski, Sijy O’Dell, Bushra Wali, Madison Ellis, Sucheta Godbole, Farida Laboune, Amy R. Henry, I-Ting Teng, Danyi Wang, Lingshu Wang, Qiong Zhou, Serge Zouantchangadou, Alex Van Ry, Mark G. Lewis, Hanne Andersen, Peter D. Kwong, David T. Curiel, Mario Roederer, Martha C. Nason, Kathryn E. Foulds, Mehul S. Suthar, Michael S. Diamond, Daniel C. Douek, Robert A. Seder","doi":"10.1038/s41590-024-01951-5","DOIUrl":"10.1038/s41590-024-01951-5","url":null,"abstract":"A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1–BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG and IgA responses and, unlike the intramuscular mRNA vaccine, induced spike-specific B cells in the lungs. IgG, IgA and T cell responses correlated with protection in the lungs, whereas mucosal IgA alone correlated with upper airway protection. This study highlights differential mucosal and serum correlates of protection and how mucosal vaccines can durably prevent infection against SARS-CoV-2. Seder and colleagues show that mucosal adenoviral-vectored vaccine boosting durably prevents infection in nonhuman primates of the highly transmissible, heterologous XBB.1.16 strain of SARS-CoV-2.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01951-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123528","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}