Timothy J. Wells, Tyron Esposito, Ian R. Henderson, Larisa I. Labzin
{"title":"Mechanisms of antibody-dependent enhancement of infectious disease","authors":"Timothy J. Wells, Tyron Esposito, Ian R. Henderson, Larisa I. Labzin","doi":"10.1038/s41577-024-01067-9","DOIUrl":null,"url":null,"abstract":"Antibody-dependent enhancement (ADE) of infectious disease is a phenomenon whereby host antibodies increase the severity of an infection. It is well established in viral infections but ADE also has an underappreciated role during bacterial, fungal and parasitic infections. ADE can occur during both primary infections and re-infections with the same or a related pathogen; therefore, understanding the underlying mechanisms of ADE is critical for understanding the pathogenesis and progression of many infectious diseases. Here, we review the four distinct mechanisms by which antibodies increase disease severity during an infection. We discuss the most established mechanistic explanation for ADE, where cross-reactive, disease-enhancing antibodies bound to pathogens interact with Fc receptors, thereby enhancing pathogen entry or replication, ultimately increasing the total pathogen load. Additionally, we explore how some pathogenic antibodies can shield bacteria from complement-dependent killing, thereby enhancing bacterial survival. We interrogate the molecular mechanisms by which antibodies can amplify inflammation to drive severe disease, even in the absence of increased pathogen replication. We also examine emerging roles for autoantibodies in enhancing the pathogenesis of infectious diseases. Finally, we discuss how we can leverage these insights to improve vaccine design and future treatments for infectious diseases. This Review discusses the different mechanisms of antibody-dependent enhancement (ADE) of infectious disease, including how antibodies can increase the pathogen load, protect bacteria from the immune system and amplify inflammation. The authors also highlight the role of autoantibodies and consider how a better understanding of ADE can be used to improve vaccines and treatments for infectious diseases.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"1-16"},"PeriodicalIF":67.7000,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41577-024-01067-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Antibody-dependent enhancement (ADE) of infectious disease is a phenomenon whereby host antibodies increase the severity of an infection. It is well established in viral infections but ADE also has an underappreciated role during bacterial, fungal and parasitic infections. ADE can occur during both primary infections and re-infections with the same or a related pathogen; therefore, understanding the underlying mechanisms of ADE is critical for understanding the pathogenesis and progression of many infectious diseases. Here, we review the four distinct mechanisms by which antibodies increase disease severity during an infection. We discuss the most established mechanistic explanation for ADE, where cross-reactive, disease-enhancing antibodies bound to pathogens interact with Fc receptors, thereby enhancing pathogen entry or replication, ultimately increasing the total pathogen load. Additionally, we explore how some pathogenic antibodies can shield bacteria from complement-dependent killing, thereby enhancing bacterial survival. We interrogate the molecular mechanisms by which antibodies can amplify inflammation to drive severe disease, even in the absence of increased pathogen replication. We also examine emerging roles for autoantibodies in enhancing the pathogenesis of infectious diseases. Finally, we discuss how we can leverage these insights to improve vaccine design and future treatments for infectious diseases. This Review discusses the different mechanisms of antibody-dependent enhancement (ADE) of infectious disease, including how antibodies can increase the pathogen load, protect bacteria from the immune system and amplify inflammation. The authors also highlight the role of autoantibodies and consider how a better understanding of ADE can be used to improve vaccines and treatments for infectious diseases.
期刊介绍:
Nature Reviews Immunology is a journal that provides comprehensive coverage of all areas of immunology, including fundamental mechanisms and applied aspects. It has two international standard serial numbers (ISSN): 1474-1733 for print and 1474-1741 for online. In addition to review articles, the journal also features recent developments and new primary papers in the field, as well as reflections on influential people, papers, and events in the development of immunology. The subjects covered by Nature Reviews Immunology include allergy and asthma, autoimmunity, antigen processing and presentation, apoptosis and cell death, chemokines and chemokine receptors, cytokines and cytokine receptors, development and function of cells of the immune system, haematopoiesis, infection and immunity, immunotherapy, innate immunity, mucosal immunology and the microbiota, regulation of the immune response, signalling in the immune system, transplantation, tumour immunology and immunotherapy, and vaccine development.