Pub Date : 2024-06-01DOI: 10.1146/annurev-immunol-090222-110227
Bruno Hernaez, Antonio Alcamí
Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit signaling pathways within the infected cell. A unique feature of poxviruses is the production of secreted proteins that mimic cytokines and cytokine receptors, acting as decoy receptors to neutralize the activity of cytokines and chemokines. The capacity of these proteins to evade cellular immune responses by inhibiting cytokine activation is complemented by poxviruses' strategies to block natural killer cells and cytotoxic T cells, often through interfering with antigen presentation pathways. Mechanisms that target complement activation are also encoded by poxviruses. Virus-encoded proteins that target immune molecules and pathways play a major role in immune modulation, and their contribution to viral pathogenesis, facilitating virus replication or preventing immunopathology, is discussed.
痘病毒进化出了一系列逃避免疫反应的机制,我们将概述不同的免疫调节策略。痘病毒会阻止识别引发免疫反应的病毒 DNA,并抑制感染细胞内的信号通路。痘病毒的一个独特特征是产生模拟细胞因子和细胞因子受体的分泌蛋白,作为诱饵受体中和细胞因子和趋化因子的活性。痘病毒通常通过干扰抗原递呈途径来阻断自然杀伤细胞和细胞毒性 T 细胞,这与痘病毒通过抑制细胞因子活化来逃避细胞免疫反应的策略相辅相成。痘病毒还编码了针对补体激活的机制。针对免疫分子和免疫途径的病毒编码蛋白在免疫调节中发挥着重要作用,本文讨论了它们对病毒发病机制的贡献,即促进病毒复制或预防免疫病理。
{"title":"Poxvirus Immune Evasion.","authors":"Bruno Hernaez, Antonio Alcamí","doi":"10.1146/annurev-immunol-090222-110227","DOIUrl":"https://doi.org/10.1146/annurev-immunol-090222-110227","url":null,"abstract":"<p><p>Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit signaling pathways within the infected cell. A unique feature of poxviruses is the production of secreted proteins that mimic cytokines and cytokine receptors, acting as decoy receptors to neutralize the activity of cytokines and chemokines. The capacity of these proteins to evade cellular immune responses by inhibiting cytokine activation is complemented by poxviruses' strategies to block natural killer cells and cytotoxic T cells, often through interfering with antigen presentation pathways. Mechanisms that target complement activation are also encoded by poxviruses. Virus-encoded proteins that target immune molecules and pathways play a major role in immune modulation, and their contribution to viral pathogenesis, facilitating virus replication or preventing immunopathology, is discussed.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465850","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}
Pub Date : 2024-06-01Epub Date: 2024-06-14DOI: 10.1146/annurev-immunol-083122-035233
Abena K Kwaa, Joel N Blankson
Elite controllers are a heterogeneous group of people living with HIV who control viral replication without antiretroviral therapy. There is substantial evidence that at least some elite controllers are infected with replication-competent virus, thus they may serve as a model of a functional cure of HIV. The mechanisms responsible for virologic control have been actively studied. The most objective data support CD8+ T cell-based mechanisms of control, but other immune responses, mediated by antibodies and natural killer cells, may also play a role in controlling viral replication. In this article, we review the evidence for different mechanisms of immune control in these remarkable individuals.
{"title":"Immune Responses in Controllers of HIV Infection.","authors":"Abena K Kwaa, Joel N Blankson","doi":"10.1146/annurev-immunol-083122-035233","DOIUrl":"10.1146/annurev-immunol-083122-035233","url":null,"abstract":"<p><p>Elite controllers are a heterogeneous group of people living with HIV who control viral replication without antiretroviral therapy. There is substantial evidence that at least some elite controllers are infected with replication-competent virus, thus they may serve as a model of a functional cure of HIV. The mechanisms responsible for virologic control have been actively studied. The most objective data support CD8+ T cell-based mechanisms of control, but other immune responses, mediated by antibodies and natural killer cells, may also play a role in controlling viral replication. In this article, we review the evidence for different mechanisms of immune control in these remarkable individuals.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41189502","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}
Pub Date : 2024-06-01Epub Date: 2024-06-14DOI: 10.1146/annurev-immunol-090222-101050
Corey N Miller, Michael R Waterfield, James M Gardner, Mark S Anderson
The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced single-cell genomics. We briefly describe the role of human genetics in the discovery of Aire, as well as insights into its function gained from genotype-phenotype correlations and the spectrum of Aire-associated autoimmunity-including insights from patients with Aire mutations with broad and diverse implications for human health. We then highlight emerging trends in Aire biology, focusing on three topic areas. First, we discuss medullary thymic epithelial diversity and the role of Aire in thymic epithelial development. Second, we highlight recent developments regarding the molecular mechanisms of Aire and its binding partners. Finally, we describe the rapidly evolving biology of the identity and function of extrathymic Aire-expressing cells (eTACs), and a novel eTAC subset called Janus cells, as well as their potential roles in immune homeostasis.
{"title":"Aire in Autoimmunity.","authors":"Corey N Miller, Michael R Waterfield, James M Gardner, Mark S Anderson","doi":"10.1146/annurev-immunol-090222-101050","DOIUrl":"10.1146/annurev-immunol-090222-101050","url":null,"abstract":"<p><p>The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced single-cell genomics. We briefly describe the role of human genetics in the discovery of Aire, as well as insights into its function gained from genotype-phenotype correlations and the spectrum of Aire-associated autoimmunity-including insights from patients with Aire mutations with broad and diverse implications for human health. We then highlight emerging trends in Aire biology, focusing on three topic areas. First, we discuss medullary thymic epithelial diversity and the role of Aire in thymic epithelial development. Second, we highlight recent developments regarding the molecular mechanisms of Aire and its binding partners. Finally, we describe the rapidly evolving biology of the identity and function of extrathymic Aire-expressing cells (eTACs), and a novel eTAC subset called Janus cells, as well as their potential roles in immune homeostasis.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740280","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}
Pub Date : 2024-06-01Epub Date: 2024-06-14DOI: 10.1146/annurev-immunol-052523-015141
Doureradjou Peroumal, Partha S Biswas
The kidneys are life-sustaining organs that are vital to removing waste from our bodies. Because of their anatomic position and high blood flow, the kidneys are vulnerable to damage due to infections and autoinflammatory conditions. Even now, our knowledge of immune responses in the kidney is surprisingly rudimentary. Studying kidney-specific immune events is challenging because of the poor regenerative capacity of the nephrons, accumulation of uremic toxins, and hypoxia- and arterial blood pressure-mediated changes, all of which have unexpected positive or negative impacts on the immune response in the kidney. Kidney-specific defense confers protection against pathogens. On the other hand, unresolved inflammation leads to kidney damage and fibrosis. Interleukin-17 is a proinflammatory cytokine that has been linked to immunity against pathogens and pathogenesis of autoinflammatory diseases. In this review, we discuss current knowledge of IL-17 activities in the kidney in the context of infections, autoinflammatory diseases, and renal fibrosis.
{"title":"Kidney-Specific Interleukin-17 Responses During Infection and Injury.","authors":"Doureradjou Peroumal, Partha S Biswas","doi":"10.1146/annurev-immunol-052523-015141","DOIUrl":"10.1146/annurev-immunol-052523-015141","url":null,"abstract":"<p><p>The kidneys are life-sustaining organs that are vital to removing waste from our bodies. Because of their anatomic position and high blood flow, the kidneys are vulnerable to damage due to infections and autoinflammatory conditions. Even now, our knowledge of immune responses in the kidney is surprisingly rudimentary. Studying kidney-specific immune events is challenging because of the poor regenerative capacity of the nephrons, accumulation of uremic toxins, and hypoxia- and arterial blood pressure-mediated changes, all of which have unexpected positive or negative impacts on the immune response in the kidney. Kidney-specific defense confers protection against pathogens. On the other hand, unresolved inflammation leads to kidney damage and fibrosis. Interleukin-17 is a proinflammatory cytokine that has been linked to immunity against pathogens and pathogenesis of autoinflammatory diseases. In this review, we discuss current knowledge of IL-17 activities in the kidney in the context of infections, autoinflammatory diseases, and renal fibrosis.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420222","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}
Pub Date : 2024-06-01Epub Date: 2024-06-14DOI: 10.1146/annurev-immunol-090222-100246
Ainsley Lockhart, Daniel Mucida, Angelina M Bilate
The intestinal epithelium, which segregates the highly stimulatory lumen from the underlying tissue, harbors one of the largest lymphocyte populations in the body, intestinal intraepithelial lymphocytes (IELs). IELs must balance tolerance, resistance, and tissue protection to maintain epithelial homeostasis and barrier integrity. This review discusses the ontogeny, environmental imprinting, T cell receptor (TCR) repertoire, and function of intestinal IELs. Despite distinct developmental pathways, IEL subsets share core traits including an epithelium-adapted profile, innate-like properties, cytotoxic potential, and limited TCR diversity. IELs also receive important developmental and functional cues through interactions with epithelial cells, microbiota, and dietary components. The restricted TCR diversity of IELs suggests that a limited set of intestinal antigens drives IEL responses, with potential functional consequences. Finally, IELs play a key role in promoting homeostatic immunity and epithelial barrier integrity but can become pathogenic upon dysregulation. Therefore, IELs represent intriguing but underexamined therapeutic targets for inflammatory diseases and cancer.
{"title":"Intraepithelial Lymphocytes of the Intestine.","authors":"Ainsley Lockhart, Daniel Mucida, Angelina M Bilate","doi":"10.1146/annurev-immunol-090222-100246","DOIUrl":"10.1146/annurev-immunol-090222-100246","url":null,"abstract":"<p><p>The intestinal epithelium, which segregates the highly stimulatory lumen from the underlying tissue, harbors one of the largest lymphocyte populations in the body, intestinal intraepithelial lymphocytes (IELs). IELs must balance tolerance, resistance, and tissue protection to maintain epithelial homeostasis and barrier integrity. This review discusses the ontogeny, environmental imprinting, T cell receptor (TCR) repertoire, and function of intestinal IELs. Despite distinct developmental pathways, IEL subsets share core traits including an epithelium-adapted profile, innate-like properties, cytotoxic potential, and limited TCR diversity. IELs also receive important developmental and functional cues through interactions with epithelial cells, microbiota, and dietary components. The restricted TCR diversity of IELs suggests that a limited set of intestinal antigens drives IEL responses, with potential functional consequences. Finally, IELs play a key role in promoting homeostatic immunity and epithelial barrier integrity but can become pathogenic upon dysregulation. Therefore, IELs represent intriguing but underexamined therapeutic targets for inflammatory diseases and cancer.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566322","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}
Pub Date : 2024-06-01Epub Date: 2024-06-14DOI: 10.1146/annurev-immunol-090222-101331
Darshan N Kasal, Lindsey M Warner, Astra S Bryant, Elia Tait Wojno, Jakob von Moltke
Gastrointestinal nematode (GIN) infection has applied significant evolutionary pressure to the mammalian immune system and remains a global economic and human health burden. Upon infection, type 2 immune sentinels activate a common antihelminth response that mobilizes and remodels the intestinal tissue for effector function; however, there is growing appreciation of the impact GIN infection also has on the distal tissue immune state. Indeed, this effect is observed even in tissues through which GINs never transit. This review highlights how GIN infection modulates systemic immunity through (a) induction of host resistance and tolerance responses, (b) secretion of immunomodulatory products, and (c) interaction with the intestinal microbiome. It also discusses the direct consequences that changes to distal tissue immunity can have for concurrent and subsequent infection, chronic noncommunicable diseases, and vaccination efficacy.
{"title":"Systemic Immune Modulation by Gastrointestinal Nematodes.","authors":"Darshan N Kasal, Lindsey M Warner, Astra S Bryant, Elia Tait Wojno, Jakob von Moltke","doi":"10.1146/annurev-immunol-090222-101331","DOIUrl":"10.1146/annurev-immunol-090222-101331","url":null,"abstract":"<p><p>Gastrointestinal nematode (GIN) infection has applied significant evolutionary pressure to the mammalian immune system and remains a global economic and human health burden. Upon infection, type 2 immune sentinels activate a common antihelminth response that mobilizes and remodels the intestinal tissue for effector function; however, there is growing appreciation of the impact GIN infection also has on the distal tissue immune state. Indeed, this effect is observed even in tissues through which GINs never transit. This review highlights how GIN infection modulates systemic immunity through (<i>a</i>) induction of host resistance and tolerance responses, (<i>b</i>) secretion of immunomodulatory products, and (<i>c</i>) interaction with the intestinal microbiome. It also discusses the direct consequences that changes to distal tissue immunity can have for concurrent and subsequent infection, chronic noncommunicable diseases, and vaccination efficacy.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566327","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}
Pub Date : 2024-06-01Epub Date: 2024-06-14DOI: 10.1146/annurev-immunol-090222-110914
Andrew Baessler, Dario A A Vignali
T cell responses must be balanced to ensure adequate protection against malignant transformation and an array of pathogens while also limiting damage to healthy cells and preventing autoimmunity. T cell exhaustion serves as a regulatory mechanism to limit the activity and effector function of T cells undergoing chronic antigen stimulation. Exhausted T cells exhibit poor proliferative potential; high inhibitory receptor expression; altered transcriptome, epigenome, and metabolism; and, most importantly, reduced effector function. While exhaustion helps to restrain damage caused by aberrant T cells in settings of autoimmune disease, it also limits the ability of cells to respond against persistent infection and cancer, leading to disease progression. Here we review the process of T cell exhaustion, detailing the key characteristics and drivers as well as highlighting our current understanding of the underlying transcriptional and epigenetic programming. We also discuss how exhaustion can be targeted to enhance T cell functionality in cancer.
T 细胞反应必须保持平衡,以确保对恶性转化和一系列病原体提供充分保护,同时限制对健康细胞的损害并防止自身免疫。T 细胞衰竭是一种调节机制,可限制长期受抗原刺激的 T 细胞的活性和效应功能。衰竭的 T 细胞增殖潜力差;抑制性受体表达高;转录组、表观基因组和新陈代谢改变;最重要的是,效应功能降低。虽然衰竭有助于抑制自身免疫性疾病中异常 T 细胞造成的损害,但它也限制了细胞应对持续感染和癌症的能力,从而导致疾病进展。在此,我们回顾了 T 细胞衰竭的过程,详细介绍了其关键特征和驱动因素,并强调了我们目前对其背后的转录和表观遗传编程的理解。我们还将讨论如何以衰竭为靶点,增强癌症中 T 细胞的功能。免疫学年刊》(Annual Review of Immunology)第42卷的最终在线出版日期预计为2024年4月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
{"title":"T Cell Exhaustion.","authors":"Andrew Baessler, Dario A A Vignali","doi":"10.1146/annurev-immunol-090222-110914","DOIUrl":"10.1146/annurev-immunol-090222-110914","url":null,"abstract":"<p><p>T cell responses must be balanced to ensure adequate protection against malignant transformation and an array of pathogens while also limiting damage to healthy cells and preventing autoimmunity. T cell exhaustion serves as a regulatory mechanism to limit the activity and effector function of T cells undergoing chronic antigen stimulation. Exhausted T cells exhibit poor proliferative potential; high inhibitory receptor expression; altered transcriptome, epigenome, and metabolism; and, most importantly, reduced effector function. While exhaustion helps to restrain damage caused by aberrant T cells in settings of autoimmune disease, it also limits the ability of cells to respond against persistent infection and cancer, leading to disease progression. Here we review the process of T cell exhaustion, detailing the key characteristics and drivers as well as highlighting our current understanding of the underlying transcriptional and epigenetic programming. We also discuss how exhaustion can be targeted to enhance T cell functionality in cancer.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080476","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}
Pub Date : 2024-06-01Epub Date: 2024-06-14DOI: 10.1146/annurev-immunol-101921-035222
Arnaud Mary, Renzo Mancuso, Michael T Heneka
Alzheimer disease (AD) is the most common neurodegenerative disease, and with no efficient curative treatment available, its medical, social, and economic burdens are expected to dramatically increase. AD is historically characterized by amyloid β (Aβ) plaques and tau neurofibrillary tangles, but over the last 25 years chronic immune activation has been identified as an important factor contributing to AD pathogenesis. In this article, we review recent and important advances in our understanding of the significance of immune activation in the development of AD. We describe how brain-resident macrophages, the microglia, are able to detect Aβ species and be activated, as well as the consequences of activated microglia in AD pathogenesis. We discuss transcriptional changes of microglia in AD, their unique heterogeneity in humans, and emerging strategies to study human microglia. Finally, we expose, beyond Aβ and microglia, the role of peripheral signals and different cell types in immune activation.
阿尔茨海默病(AD)是最常见的神经退行性疾病,由于没有有效的治疗方法,预计其医疗、社会和经济负担将急剧增加。淀粉样β(Aβ)斑块和tau神经纤维缠结是阿尔茨海默病的历史特征,但在过去的25年中,慢性免疫激活已被确定为导致阿尔茨海默病发病的一个重要因素。在这篇文章中,我们回顾了最近在理解免疫激活在AD发病中的意义方面取得的重要进展。我们描述了大脑驻留的巨噬细胞--小胶质细胞如何能够检测到 Aβ 物种并被激活,以及激活的小胶质细胞在 AD 发病机制中的后果。我们讨论了 AD 中小胶质细胞的转录变化、它们在人类中的独特异质性以及研究人类小胶质细胞的新兴策略。最后,除了 Aβ 和小胶质细胞外,我们还揭示了外周信号和不同细胞类型在免疫激活中的作用。免疫学年刊》(Annual Review of Immunology)第42卷的最终在线出版日期预计为2024年4月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
{"title":"Immune Activation in Alzheimer Disease.","authors":"Arnaud Mary, Renzo Mancuso, Michael T Heneka","doi":"10.1146/annurev-immunol-101921-035222","DOIUrl":"10.1146/annurev-immunol-101921-035222","url":null,"abstract":"<p><p>Alzheimer disease (AD) is the most common neurodegenerative disease, and with no efficient curative treatment available, its medical, social, and economic burdens are expected to dramatically increase. AD is historically characterized by amyloid β (Aβ) plaques and tau neurofibrillary tangles, but over the last 25 years chronic immune activation has been identified as an important factor contributing to AD pathogenesis. In this article, we review recent and important advances in our understanding of the significance of immune activation in the development of AD. We describe how brain-resident macrophages, the microglia, are able to detect Aβ species and be activated, as well as the consequences of activated microglia in AD pathogenesis. We discuss transcriptional changes of microglia in AD, their unique heterogeneity in humans, and emerging strategies to study human microglia. Finally, we expose, beyond Aβ and microglia, the role of peripheral signals and different cell types in immune activation.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995423","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}
Pub Date : 2024-06-01DOI: 10.1146/annurev-immunol-083122-043545
R K Subbarao Malireddi, Bhesh Raj Sharma, Thirumala-Devi Kanneganti
The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. The innate immune system is the first line of defense against infections, including the detection and response to SARS-CoV-2. Here, we discuss the innate immune mechanisms that sense coronaviruses, with a focus on SARS-CoV-2 infection and how these protective responses can become detrimental in severe cases of COVID-19, contributing to cytokine storm, inflammation, long-COVID, and other complications. We also highlight the complex cross talk among cytokines and the cellular components of the innate immune system, which can aid in viral clearance but also contribute to inflammatory cell death, cytokine storm, and organ damage in severe COVID-19 pathogenesis. Furthermore, we discuss how SARS-CoV-2 evades key protective innate immune mechanisms to enhance its virulence and pathogenicity, as well as how innate immunity can be therapeutically targeted as part of the vaccination and treatment strategy. Overall, we highlight how a comprehensive understanding of innate immune mechanisms has been crucial in the fight against SARS-CoV-2 infections and the development of novel host-directed immunotherapeutic strategies for various diseases.
{"title":"Innate Immunity in Protection and Pathogenesis During Coronavirus Infections and COVID-19.","authors":"R K Subbarao Malireddi, Bhesh Raj Sharma, Thirumala-Devi Kanneganti","doi":"10.1146/annurev-immunol-083122-043545","DOIUrl":"10.1146/annurev-immunol-083122-043545","url":null,"abstract":"<p><p>The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. The innate immune system is the first line of defense against infections, including the detection and response to SARS-CoV-2. Here, we discuss the innate immune mechanisms that sense coronaviruses, with a focus on SARS-CoV-2 infection and how these protective responses can become detrimental in severe cases of COVID-19, contributing to cytokine storm, inflammation, long-COVID, and other complications. We also highlight the complex cross talk among cytokines and the cellular components of the innate immune system, which can aid in viral clearance but also contribute to inflammatory cell death, cytokine storm, and organ damage in severe COVID-19 pathogenesis. Furthermore, we discuss how SARS-CoV-2 evades key protective innate immune mechanisms to enhance its virulence and pathogenicity, as well as how innate immunity can be therapeutically targeted as part of the vaccination and treatment strategy. Overall, we highlight how a comprehensive understanding of innate immune mechanisms has been crucial in the fight against SARS-CoV-2 infections and the development of novel host-directed immunotherapeutic strategies for various diseases.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465825","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}
Pub Date : 2024-06-01Epub Date: 2024-06-14DOI: 10.1146/annurev-immunol-080223-044610
Isaac F López-Moyado, Myunggon Ko, Patrick G Hogan, Anjana Rao
Ten-eleven translocation (TET) proteins are iron-dependent and α-ketoglutarate-dependent dioxygenases that sequentially oxidize the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). All three epigenetic modifications are intermediates in DNA demethylation. TET proteins are recruited by transcription factors and by RNA polymerase II to modify 5mC at enhancers and gene bodies, thereby regulating gene expression during development, cell lineage specification, and cell activation. It is not yet clear, however, how the established biochemical activities of TET enzymes in oxidizing 5mC and mediating DNA demethylation relate to the known association of TET deficiency with inflammation, clonal hematopoiesis, and cancer. There are hints that the ability of TET deficiency to promote cell proliferation in a signal-dependent manner may be harnessed for cancer immunotherapy. In this review, we draw upon recent findings in cells of the immune system to illustrate established as well as emerging ideas of how TET proteins influence cellular function.
十-十一转位(TET)蛋白是一种铁依赖型和α-酮戊二酸依赖型二氧 化酶,能依次将 5-甲基胞嘧啶(5mC)的甲基氧化成 5-羟甲基胞嘧啶(5hmC)、5-甲酰基胞嘧啶(5fC)和 5-羧基胞嘧啶(5caC)。这三种表观遗传修饰都是 DNA 去甲基化的中间产物。TET 蛋白受转录因子和 RNA 聚合酶 II 的招募,对增强子和基因体上的 5mC 进行修饰,从而在发育、细胞系分化和细胞活化过程中调节基因表达。然而,目前还不清楚 TET 酶氧化 5mC 和介导 DNA 去甲基化的既定生化活动与已知的 TET 缺乏症与炎症、克隆造血和癌症之间的关系。有迹象表明,TET 缺乏症以信号依赖方式促进细胞增殖的能力可用于癌症免疫疗法。在这篇综述中,我们借鉴了最近在免疫系统细胞中的发现,以说明 TET 蛋白如何影响细胞功能的既有观点和新观点。免疫学年刊》(Annual Review of Immunology)第 42 卷的最终在线出版日期预计为 2024 年 4 月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
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