Palmira Barreira-Silva, Yilong Lian, Stefan H. E. Kaufmann, Pedro Moura-Alves
{"title":"The role of the AHR in host–pathogen interactions","authors":"Palmira Barreira-Silva, Yilong Lian, Stefan H. E. Kaufmann, Pedro Moura-Alves","doi":"10.1038/s41577-024-01088-4","DOIUrl":"10.1038/s41577-024-01088-4","url":null,"abstract":"Host–microorganism encounters take place in many different ways and with different types of outcomes. Three major types of microorganisms need to be distinguished: (1) pathogens that cause harm to the host and must be controlled; (2) environmental microorganisms that can be ignored but must be controlled at higher abundance; and (3) symbiotic microbiota that require support by the host. Recent evidence indicates that the aryl hydrocarbon receptor (AHR) senses and initiates signalling and gene expression in response to a plethora of microorganisms and infectious conditions. It was originally identified as a receptor that binds xenobiotics. However, it was subsequently found to have a critical role in numerous biological processes, including immunity and inflammation and was recently classified as a pattern recognition receptor. Here we review the role of the AHR in host–pathogen interactions, focusing on AHR sensing of different microbial classes, the ligands involved, responses elicited and disease outcomes. Moreover, we explore the therapeutic potential of targeting the AHR in the context of infection. The aryl hydrocarbon receptor (AHR) can sense and initiate immune responses to many different infectious organisms. Here, Moura-Alves and colleagues review the role of the AHR in host–pathogen interactions and explore the therapeutic potential of targeting the AHR in the context of different infectious diseases.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"178-194"},"PeriodicalIF":67.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439691","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":"Fever affects T cell fate","authors":"Lucy Bird","doi":"10.1038/s41577-024-01101-w","DOIUrl":"10.1038/s41577-024-01101-w","url":null,"abstract":"Febrile temperatures disrupt metabolism and induce DNA damage disproportionately in T helper 1 cell subsets. Cells that survive apoptosis and adapt by increasing their mitochondrial mass and DNA damage responses gain enhanced effector functions.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"778-778"},"PeriodicalIF":67.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405142","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}
Robert Thimme, Antonio Bertoletti, Matteo Iannacone
{"title":"Beyond exhaustion: the unique characteristics of CD8+ T cell dysfunction in chronic HBV infection","authors":"Robert Thimme, Antonio Bertoletti, Matteo Iannacone","doi":"10.1038/s41577-024-01097-3","DOIUrl":"10.1038/s41577-024-01097-3","url":null,"abstract":"CD8+ T cells are crucial in controlling infection with hepatitis B virus (HBV) but are functionally impaired during chronic HBV infection. Traditionally, these functional deficits have been associated with classical T cell exhaustion due to persistent antigenic stimulation. However, recent findings challenge this concept, emphasizing the multifactorial nature of T cell dysfunction in HBV infection. CD8+ T cells are functionally impaired during chronic HBV infection. Recent findings from preclinical models and studies of chronically infected humans have revealed surprising insights into the nature of the T cell dysfunction, which may open new avenues for therapeutic intervention.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"775-776"},"PeriodicalIF":67.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374142","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}
Ananda Shanti Mirchandani, Manuel Alejandro Sanchez-Garcia, Sarah Ruth Walmsley
{"title":"How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia","authors":"Ananda Shanti Mirchandani, Manuel Alejandro Sanchez-Garcia, Sarah Ruth Walmsley","doi":"10.1038/s41577-024-01087-5","DOIUrl":"10.1038/s41577-024-01087-5","url":null,"abstract":"Most eukaryotes require oxygen for their survival and, with increasing multicellular complexity, oxygen availability and delivery rates vary across the tissues of complex organisms. In humans, healthy tissues have markedly different oxygen gradients, ranging from the hypoxic environment of the bone marrow (where our haematopoietic stem cells reside) to the lungs and their alveoli, which are among the most oxygenated areas of the body. Immune cells are therefore required to adapt to varying oxygen availability as they move from the bone marrow to peripheral organs to mediate their effector functions. These changing oxygen gradients are exaggerated during inflammation, where oxygenation is often depleted owing to alterations in tissue perfusion and increased cellular activity. As such, it is important to consider the effects of oxygenation on shaping the immune response during tissue homeostasis and disease conditions. In this Review, we address the relevance of both physiological oxygenation (physioxia) and disease-associated hypoxia (where cellular oxygen demand outstrips supply) for immune cell functions, discussing the relevance of hypoxia for immune responses in the settings of tissue homeostasis, inflammation, infection, cancer and disease immunotherapy. Oxygen levels vary throughout the body and immune cells must adapt to these changes, both during homeostasis and in disease. Here, the authors discuss the impact of physiological subatmospheric oxygen levels (physioxia) as well as disease-related hypoxia on immune cell responses. They consider the therapeutic relevance of understanding how oxygenation affects immune responses in various diseases, including tuberculosis, COVID-19 and cancer.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 3","pages":"161-177"},"PeriodicalIF":67.7,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329715","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}
Satish Kumar Tiwari, Wei Jie Wong, Marco Moreira, Claudia Pasqualini, Florent Ginhoux
{"title":"Induced pluripotent stem cell-derived macrophages as a platform for modelling human disease","authors":"Satish Kumar Tiwari, Wei Jie Wong, Marco Moreira, Claudia Pasqualini, Florent Ginhoux","doi":"10.1038/s41577-024-01081-x","DOIUrl":"10.1038/s41577-024-01081-x","url":null,"abstract":"Macrophages are innate immune cells that are present in essentially all tissues, where they have vital roles in tissue development, homeostasis and pathogenesis. The importance of macrophages in tissue function is reflected by their association with various human diseases, and studying macrophage functions in both homeostasis and pathological tissue settings is a promising avenue for new targeted therapies that will improve human health. The ability to generate macrophages from induced pluripotent stem (iPS) cells has revolutionized macrophage biology, with the generation of iPS cell-derived macrophages (iMacs) providing unlimited access to genotype-specific cells that can be used to model various human diseases involving macrophage dysregulation. Such disease modelling is achieved by generating iPS cells from patient-derived cells carrying disease-related mutations or by introducing mutations into iPS cells from healthy donors using CRISPR–Cas9 technology. These iMacs that carry disease-related mutations can be used to study the aetiology of the particular disease in vitro. To achieve more physiological relevance, iMacs can be co-cultured in 2D systems with iPS cell-derived cells or in 3D systems with iPS cell-derived organoids. Here, we discuss the studies that have attempted to model various human diseases using iMacs, highlighting how these have advanced our knowledge about the role of macrophages in health and disease. Macrophages are associated with many human diseases but are challenging to study in vivo. Here, Ginhoux and colleagues discuss how iMacs — macrophages generated from induced pluripotent stem (iPS) cells — can enable disease modelling, including through the use of patient-derived iPS cells and 3D organoid co-culture systems. Ultimately, these iMac-based approaches can improve our understanding of macrophage biology in both health and disease.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 2","pages":"108-124"},"PeriodicalIF":67.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328642","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":"An inhibitory PRR reels in the neutrophil response to NETs","authors":"Yvonne Bordon","doi":"10.1038/s41577-024-01096-4","DOIUrl":"10.1038/s41577-024-01096-4","url":null,"abstract":"MICL regulates neutrophil responses by serving as an inhibitory pattern-recognition receptor for NETs.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"779-779"},"PeriodicalIF":67.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313714","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":"Publisher Correction: Role of thymic stromal lymphopoietin in allergy and beyond","authors":"Risa Ebina-Shibuya, Warren J. Leonard","doi":"10.1038/s41577-024-01094-6","DOIUrl":"10.1038/s41577-024-01094-6","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"846-846"},"PeriodicalIF":67.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41577-024-01094-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314067","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":"Understanding vertebrate immunity through comparative immunology","authors":"Thomas Boehm","doi":"10.1038/s41577-024-01083-9","DOIUrl":"10.1038/s41577-024-01083-9","url":null,"abstract":"Evolutionary immunology has entered a new era. Classical studies, using just a handful of model animal species, combined with clinical observations, provided an outline of how innate and adaptive immunity work together to ensure tissue homeostasis and to coordinate the fight against infections. However, revolutionary advances in cellular and molecular biology, genomics and methods of genetic modification now offer unprecedented opportunities. They provide immunologists with the possibility to consider, at unprecedented scale, the impact of the astounding phenotypic diversity of vertebrates on immune system function. This Perspective is intended to highlight some of the many interesting, but largely unexplored, biological phenomena that are related to immune function among the roughly 60,000 existing vertebrate species. Importantly, hypotheses arising from such wide-ranging comparative studies can be tested in representative and genetically tractable species. The emerging general principles and the discovery of their evolutionarily selected variations may inspire the future development of novel therapeutic strategies for human immune disorders. Technological advances in cellular and molecular immunology are providing unprecedented new insights into evolutionary immunology. This Perspective highlights new insights into the immune systems of different vertebrate species and discusses emerging general principles of immune system function.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 2","pages":"141-152"},"PeriodicalIF":67.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313715","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":"Mitochondrial tonic for adoptive T cell therapies","authors":"Kirsty Minton","doi":"10.1038/s41577-024-01095-5","DOIUrl":"10.1038/s41577-024-01095-5","url":null,"abstract":"A study in Cell describes a platform to supply exogenous mitochondria to CD8+ T cells via nanotubes, which boosts their antitumour efficacy.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"777-777"},"PeriodicalIF":67.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275155","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":"Antigen presentation for central tolerance induction","authors":"Ludger Klein, Elisabetta Petrozziello","doi":"10.1038/s41577-024-01076-8","DOIUrl":"10.1038/s41577-024-01076-8","url":null,"abstract":"The extent of central T cell tolerance is determined by the diversity of self-antigens that developing thymocytes ‘see’ on thymic antigen-presenting cells (APCs). Here, focusing on insights from the past decade, we review the functional adaptations of medullary thymic epithelial cells, thymic dendritic cells and thymic B cells for the purpose of tolerance induction. Their distinct cellular characteristics range from unconventional phenomena, such as promiscuous gene expression or mimicry of peripheral cell types, to strategic positioning in distinct microenvironments and divergent propensities to preferentially access endogenous or exogenous antigen pools. We also discuss how ‘tonic’ inflammatory signals in the thymic microenvironment may extend the intrathymically visible ‘self’ to include autoantigens that are otherwise associated with highly immunogenic peripheral environments. For effective central T cell tolerance, developing thymocytes must encounter a diverse range of self-antigens presented by various thymic cells. Here, the authors describe how medullary thymic epithelial cells, dendritic cells and B cells are uniquely adapted through promiscuous gene expression, strategic positioning and inflammatory signals, which shape the peptide–MHC ligandomes and extend self-antigen visibility in the thymic microenvironment.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 1","pages":"57-72"},"PeriodicalIF":67.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236286","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}