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Tripping the wire: sensing of viral protease activity by CARD8 and NLRP1 inflammasomes 绊倒电线：通过CARD8和NLRP1炎症小体感知病毒蛋白酶活性。
IF 7 2区 医学
Current Opinion in Immunology Pub Date : 2023-08-01 DOI: 10.1016/j.coi.2023.102354
Lennice K Castro, Matthew D Daugherty
{"title":"Tripping the wire: sensing of viral protease activity by CARD8 and NLRP1 inflammasomes","authors":"Lennice K Castro,&nbsp;Matthew D Daugherty","doi":"10.1016/j.coi.2023.102354","DOIUrl":"10.1016/j.coi.2023.102354","url":null,"abstract":"<div><p>Host innate immune sensors are vital for the initial detection of pathogen infection. Such sensors thus need to constantly adapt in escalating evolutionary arms races with pathogens. Recently, two inflammasome-forming proteins, CARD8 and NLRP1, have emerged as innate immune sensors for the enzymatic activity of virus-encoded proteases. When cleaved within a rapidly evolving ‘tripwire’ region, CARD8 and NLRP1 assemble into inflammasomes that initiate pyroptotic cell death and pro-inflammatory cytokine release as a form of effector-triggered immunity. Short motifs in the CARD8 and NLRP1 tripwires mimic the protease-specific cleavage sites of picornaviruses, coronaviruses, and HIV-1, providing virus-specific sensing that can rapidly change between closely related hosts and within the human population. Recent work highlights the evolutionary arms races between viral proteases and NLRP1 and CARD8, including insights into the mechanisms of inflammasome activation, host diversity of viral sensing, and means that viruses have evolved to avoid tripping the wire.</p></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"83 ","pages":"Article 102354"},"PeriodicalIF":7.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528193/pdf/nihms-1918765.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
CD1 displays its own negative regulators CD1显示出自己的负调节因子。
IF 7 2区 医学
Current Opinion in Immunology Pub Date : 2023-08-01 DOI: 10.1016/j.coi.2023.102339
Adam Shahine , Ildiko Van Rhijn , Jamie Rossjohn , D. Branch Moody
{"title":"CD1 displays its own negative regulators","authors":"Adam Shahine ,&nbsp;Ildiko Van Rhijn ,&nbsp;Jamie Rossjohn ,&nbsp;D. Branch Moody","doi":"10.1016/j.coi.2023.102339","DOIUrl":"10.1016/j.coi.2023.102339","url":null,"abstract":"<div><p><span><span>After two decades of the study of lipid antigens that activate CD1-restricted T cells, new studies show how autoreactive αβ T-cell receptors (TCRs) can directly recognize the outer surface of </span>CD1 proteins in ways that are lipid-agnostic. Most recently, this lipid agnosticism has turned to negativity, with the discovery of natural CD1 ligands that dominantly negatively block autoreactive αβ TCR binding to CD1a and CD1d. This review highlights the basic differences between positive and negative regulation of cellular systems. We outline strategies to discover lipid inhibitors of CD1-reactive T cells, whose roles </span><em>in vivo</em><span> are becoming clear, especially in CD1-mediated skin disease.</span></p></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"83 ","pages":"Article 102339"},"PeriodicalIF":7.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9943785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Molecular insights into metabolite antigen recognition by mucosal-associated invariant T cells 黏膜相关不变T细胞识别代谢产物抗原的分子见解
IF 7 2区 医学
Current Opinion in Immunology Pub Date : 2023-08-01 DOI: 10.1016/j.coi.2023.102351
Wael Awad , Lisa Ciacchi , James McCluskey , David P Fairlie , Jamie Rossjohn
{"title":"Molecular insights into metabolite antigen recognition by mucosal-associated invariant T cells","authors":"Wael Awad ,&nbsp;Lisa Ciacchi ,&nbsp;James McCluskey ,&nbsp;David P Fairlie ,&nbsp;Jamie Rossjohn","doi":"10.1016/j.coi.2023.102351","DOIUrl":"10.1016/j.coi.2023.102351","url":null,"abstract":"<div><p><span>Metabolite-based T-cell immunity is emerging as a major player in antimicrobial immunity, autoimmunity, and cancer. Here, small-molecule metabolites were identified to be captured and presented by the major histocompatibility complex class-I-related molecule (MR1) to </span>T cells<span>, namely mucosal-associated invariant T cells (MAIT) and diverse MR1-restricted T cells. Both MR1 and MAIT are evolutionarily conserved in many mammals, suggesting important roles in host immunity. Rational chemical modifications of these naturally occurring metabolites, termed altered metabolite ligands (AMLs), have advanced our understanding of the molecular correlates of MAIT T cell receptor (TCR)-MR1 recognition. This review provides a generalized framework for metabolite recognition and modulation of MAIT cells.</span></p></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"83 ","pages":"Article 102351"},"PeriodicalIF":7.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9943796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond natural biology: rewiring cellular networks to study innate immunity 超越自然生物学：重新连接细胞网络以研究先天免疫。
IF 7 2区 医学
Current Opinion in Immunology Pub Date : 2023-08-01 DOI: 10.1016/j.coi.2023.102349
Lauren M Landau, Jonathan C Kagan
{"title":"Beyond natural biology: rewiring cellular networks to study innate immunity","authors":"Lauren M Landau,&nbsp;Jonathan C Kagan","doi":"10.1016/j.coi.2023.102349","DOIUrl":"10.1016/j.coi.2023.102349","url":null,"abstract":"<div><p>Within immune cells<span><span>, microbial and self-ligands trigger pattern recognition receptors (PRRs) to nucleate and activate the signaling organelles of the immune system. Much work in this area has derived from observational biology of natural innate immune signaling. More recently, synthetic biology approaches have been used to rewire and study innate immune networks. By utilizing controllable chemical or </span>optogenetic<span> inputs, rearranging protein building blocks, or engineering signal recording circuits, synthetic biology-based techniques complement and inform studies of natural immune pathway operation. In this review, we describe recent synthetic biology-based approaches that have uncovered new insights into PRR signaling, virus-host interactions, and systemic cytokine responses.</span></span></p></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"83 ","pages":"Article 102349"},"PeriodicalIF":7.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9944084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Get into the groove! The influence of TAPBPR on cargo selection 进入最佳状态！TAPBPR对货物选择的影响
IF 7 2区 医学
Current Opinion in Immunology Pub Date : 2023-08-01 DOI: 10.1016/j.coi.2023.102346
Reem Satti , Jack L Morley , Louise H Boyle
{"title":"Get into the groove! The influence of TAPBPR on cargo selection","authors":"Reem Satti ,&nbsp;Jack L Morley ,&nbsp;Louise H Boyle","doi":"10.1016/j.coi.2023.102346","DOIUrl":"10.1016/j.coi.2023.102346","url":null,"abstract":"<div><p><span>Since the discovery of Transporter associated with antigen processing-binding protein-related (TAPBPR) over two decades ago, extensive studies have explored its function in the context of the major histocompatibility complex class-I (MHC-I) </span>antigen processing<span> and presentation pathway. As a chaperone and peptide editor, TAPBPR was recently revealed to have overlapping structural features when resolved with peptide-receptive MHC-I molecules compared with the two newly solved tapasin:MHC-I structures. Despite this, the two chaperones seem to have a unique criteria for loading high-affinity peptides on MHC-I molecules. Yet, the mechanism of action of how TAPBPR creates its distinct filter in cargo selection for peptide-receptive MHC-I molecules continues to be a subject of debate.</span></p></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"83 ","pages":"Article 102346"},"PeriodicalIF":7.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9949930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In search of the cell biology for self- versus non-self- recognition 寻找自我识别与非自我识别的细胞生物学
IF 7 2区 医学
Current Opinion in Immunology Pub Date : 2023-08-01 DOI: 10.1016/j.coi.2023.102334
Sebastien Apcher , Borek Vojtesek , Robin Fahraeus
{"title":"In search of the cell biology for self- versus non-self- recognition","authors":"Sebastien Apcher ,&nbsp;Borek Vojtesek ,&nbsp;Robin Fahraeus","doi":"10.1016/j.coi.2023.102334","DOIUrl":"10.1016/j.coi.2023.102334","url":null,"abstract":"<div><p>Several of today’s cancer treatments are based on the immune system’s capacity to detect and destroy cells expressing neoantigens on major histocompatibility class-I molecules (MHC-I). Despite this, we still do not know the cell biology behind how antigenic peptide substrates (APSs) for the MHC-I pathway are produced. Indeed, there are few research fields with so many divergent views as the one concerning the source of APSs. This is quite remarkable considering their fundamental role in the immune systems’ capacity to detect and destroy virus-infected or transformed cells. A better understanding of the processes generating APSs and how these are regulated will shed light on the evolution of self-recognition and provide new targets for therapeutic intervention. We discuss the search for the elusive source of MHC-I peptides and highlight the cell biology that is still missing to explain how they are synthesised and where they come from.</p></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"83 ","pages":"Article 102334"},"PeriodicalIF":7.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Visualising tapasin- and TAPBPR-assisted editing of major histocompatibility complex class-I immunopeptidomes 可视化tapasin和TAPBPR辅助编辑主要组织相容性复合体I类免疫肽
IF 7 2区 医学
Current Opinion in Immunology Pub Date : 2023-08-01 DOI: 10.1016/j.coi.2023.102340
Andy van Hateren , Tim Elliott
{"title":"Visualising tapasin- and TAPBPR-assisted editing of major histocompatibility complex class-I immunopeptidomes","authors":"Andy van Hateren ,&nbsp;Tim Elliott","doi":"10.1016/j.coi.2023.102340","DOIUrl":"10.1016/j.coi.2023.102340","url":null,"abstract":"<div><p>Which peptides are selected for presentation by major histocompatibility complex class-I (MHC-I) molecules is a key determinant of successful immune responses. Peptide selection is co-ordinated by the tapasin and TAP Binding PRotein (TAPBPR) proteins, which ensure MHC-I molecules preferentially acquire high-affinity-binding peptides. New structural analyses have offered insight into how tapasin achieves this function within the peptide-loading complex (PLC) (comprising the Transporter associated with Antigen Presentation (TAP) peptide transporter, tapasin–ERp57, MHC-I and calreticulin), and how TAPBPR performs a peptide editing function independently of other molecules. The new structures reveal nuances in how tapasin and TAPBPR interact with MHC-I, and how calreticulin and ERp57 complement tapasin to exploit the plasticity of MHC-I molecules to achieve peptide editing.</p></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"83 ","pages":"Article 102340"},"PeriodicalIF":7.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9943786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microevolution of Pseudomonas aeruginosa in the airways of people with cystic fibrosis 囊性纤维化患者气道中铜绿假单胞菌的微进化
IF 7 2区 医学
Current Opinion in Immunology Pub Date : 2023-08-01 DOI: 10.1016/j.coi.2023.102328
Nina Cramer , Jens Klockgether , Burkhard Tümmler
{"title":"Microevolution of Pseudomonas aeruginosa in the airways of people with cystic fibrosis","authors":"Nina Cramer ,&nbsp;Jens Klockgether ,&nbsp;Burkhard Tümmler","doi":"10.1016/j.coi.2023.102328","DOIUrl":"10.1016/j.coi.2023.102328","url":null,"abstract":"<div><p>The chronic infections of cystic fibrosis (CF) airways with <em>Pseudomonas aeruginosa</em> are a paradigm of how environmental bacteria can conquer, adapt, and persist in an atypical habitat and successfully evade defense mechanisms and chemotherapy in a susceptible host. The within-host evolution of intraclonal diversity has been examined by whole-genome sequencing, phenotyping, and competitive fitness experiments of serial <em>P. aeruginosa</em> isolates collected from CF airways since onset of colonization for a period of up to 40 years. The spectrum of de novo mutations and the adaptation of phenotype and fitness of the bacterial progeny were more influenced by the living conditions in the CF lung than by the clone type of their ancestor and its genetic repertoire.</p></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"83 ","pages":"Article 102328"},"PeriodicalIF":7.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9945949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Functional flexibility and plasticity in immune control of systemic Salmonella infection 系统性沙门氏菌感染免疫控制中的功能灵活性和可塑性
IF 7 2区 医学
Current Opinion in Immunology Pub Date : 2023-08-01 DOI: 10.1016/j.coi.2023.102343
Sven Engel , Annabell Bachem , Richard A Strugnell , Andreas Strasser , Marco J Herold , Sammy Bedoui
{"title":"Functional flexibility and plasticity in immune control of systemic Salmonella infection","authors":"Sven Engel ,&nbsp;Annabell Bachem ,&nbsp;Richard A Strugnell ,&nbsp;Andreas Strasser ,&nbsp;Marco J Herold ,&nbsp;Sammy Bedoui","doi":"10.1016/j.coi.2023.102343","DOIUrl":"10.1016/j.coi.2023.102343","url":null,"abstract":"<div><p>Immunity to systemic <em>Salmonella</em><span> infection depends on multiple effector mechanisms. Lymphocyte-derived interferon gamma<span> (IFN-γ) enhances cell-intrinsic bactericidal capabilities to antagonize the hijacking of phagocytes as replicative niches for </span></span><em>Salmonella</em><span>. Programmed cell death (PCD) provides another means through which phagocytes fight against intracellular </span><em>Salmonella</em><span>. We describe remarkable levels of flexibility with which the host coordinates and adapts these responses. This involves interchangeable cellular sources of IFN-γ regulated by innate and adaptive cues, and the rewiring of PCD pathways in previously unknown ways. We discuss that such plasticity is likely the consequence of host–pathogen coevolution and raise the possibility of further functional overlap between these seemingly distinct processes.</span></p></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"83 ","pages":"Article 102343"},"PeriodicalIF":7.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10317714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent progress in type 1 classical dendritic cell cross-presentation - cytosolic, vacuolar, or both? 1型经典树突状细胞交叉呈递的最新进展——胞质、液泡还是两者兼有？
IF 7 2区 医学
Current Opinion in Immunology Pub Date : 2023-08-01 DOI: 10.1016/j.coi.2023.102350
Ray A Ohara, Kenneth M Murphy
{"title":"Recent progress in type 1 classical dendritic cell cross-presentation - cytosolic, vacuolar, or both?","authors":"Ray A Ohara,&nbsp;Kenneth M Murphy","doi":"10.1016/j.coi.2023.102350","DOIUrl":"10.1016/j.coi.2023.102350","url":null,"abstract":"<div><p>Type 1 classical dendritic cells (cDC1s) have emerged as the major antigen-presenting cell performing cross-presentation (XP) <em>in vivo</em>, but the antigen-processing pathway in this cell remains obscure. Two competing models for <em>in vivo</em><span> XP of cell-associated antigens by cDC1 include a vacuolar pathway and cytosolic pathway. A vacuolar pathway relies on directing antigens captured in vesicles toward a class I major histocompatibility complex<span> loading compartment independently of cytosolic entry. Alternate proposals invoke phagosomal rupture, either constitutive or triggered by spleen tyrosine kinase (SYK) signaling in response to C-type lectin domain family 9 member A (CLEC9A) engagement, that releases antigens into the cytosol for proteasomal degradation. The Beige and Chediak–Higashi (BEACH) protein WD repeat- and FYVE domain-containing protein 4 (WDFY4) is strictly required for XP of cell-associated antigens </span></span><em>in vivo</em>. However, the cellular mechanism for WDFY4 activity remains unknown and its requirement in XP <em>in vivo</em> is currently indifferent regarding the vacuolar versus cytosolic pathways. Here, we review the current status of these models and discuss the need for future investigation.</p></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"83 ","pages":"Article 102350"},"PeriodicalIF":7.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9943800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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