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Innate Immunity and Parkinson's Disease. 先天免疫和帕金森病。
IF 10.1 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2026-05-01 DOI: 10.1101/cshperspect.a041640
Davina B Oludipe, Xiaoqing Du, Samia Akter, Chen Zhang, R Lee Mosley, Howard E Gendelman, Susmita Sil
{"title":"Innate Immunity and Parkinson's Disease.","authors":"Davina B Oludipe, Xiaoqing Du, Samia Akter, Chen Zhang, R Lee Mosley, Howard E Gendelman, Susmita Sil","doi":"10.1101/cshperspect.a041640","DOIUrl":"10.1101/cshperspect.a041640","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of both dopaminergic and non-dopaminergic neurons associated with the accumulation of α-synuclein aggregates and signs of neuroinflammation. This inflammatory aspect of PD neuropathology has led to the hypothesis that the immune system, both adaptive and innate, contributes to the neurodegenerative process. While the adaptive immune system is discussed in detail in another article in this collection, this review focuses on the innate immune system, which includes monocytes, macrophages, microglia, and dendritic cells. We will also discuss the increasingly recognized link between genetic and immune response and the cross talk between peripheral and central immune cells, and its contribution to the overall immune response in PD. Finally, we will propose therapeutic strategies aimed at modulating immunity for neuroprotective and disease-modifying benefits in PD and related disorders.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309657","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
Update on Tuberculosis Treatment and Drug Regimens. 结核病治疗和药物方案的最新情况。
IF 10.1 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2026-05-01 DOI: 10.1101/cshperspect.a041826
Rosella Centis, Lia D'Ambrosio, Giovanni Battista Migliori
{"title":"Update on Tuberculosis Treatment and Drug Regimens.","authors":"Rosella Centis, Lia D'Ambrosio, Giovanni Battista Migliori","doi":"10.1101/cshperspect.a041826","DOIUrl":"10.1101/cshperspect.a041826","url":null,"abstract":"<p><p>Tuberculosis is an airborne infectious disease treated with combination therapeutic regimens. Adherence to long-term antituberculosis therapy is crucial to maintain adequate blood drug level. The emergence and spread of drug-resistant <i>Mycobacterium tuberculosis</i> strains is mainly favored by the inadequate medical management of patients. The therapeutic approach for drug-resistant tuberculosis is cumbersome, because of the poor, expensive, less effective, and toxic alternatives to the first-line drugs. New antituberculosis regimens have been recently approved by the health authorities shortening the duration of treatment for both drug-susceptible and drug-resistant tuberculosis drugs, including new drugs such as bedaquiline, delamanid, and pretomanid. Unfortunately, they cannot represent the definitive solution to the clinical management of drug-resistant tuberculosis forms, particularly in intermediate economy settings where the prevalence of drug-resistance is high (China, India, and Former Soviet Union countries among others). Last but not least, new evidence on the burden of posttuberculosis lung disease calls for effective prevention, treatment, and rehabilitation of this form of disease. New research and development activities are urgently needed. Public health policies are required to preserve the new and old therapeutic options.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580762","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
T Cell Differentiation in Autoimmune Type 1 Diabetes. 自身免疫性1型糖尿病的T细胞分化
IF 10.1 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2026-05-01 DOI: 10.1101/cshperspect.a041592
Andrea Schietinger, Ian T McBain, Katrina M Hawley, Svetlana Miakicheva
{"title":"T Cell Differentiation in Autoimmune Type 1 Diabetes.","authors":"Andrea Schietinger, Ian T McBain, Katrina M Hawley, Svetlana Miakicheva","doi":"10.1101/cshperspect.a041592","DOIUrl":"10.1101/cshperspect.a041592","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is a progressive T cell-mediated autoimmune disease that results from the breakdown of tolerance mechanisms in β-cell-specific T cells. Although CD8 T cells are primarily responsible for the destruction of insulin-producing β cells, intriguingly, HLA class II allelic polymorphisms confer the greatest genetic risk for the development of T1D, suggesting a critical role of CD4 T cells in disease initiation and progression. Many aspects of autoimmune T cell differentiation remain enigmatic, including where and how autoimmune CD8 and CD4 T cells arise, which molecular programs control autoimmune T cell differentiation, and how CD8 T cells sustain β-cell destruction in the face of persistent self-antigen encounter. In this work, we summarize our current understanding of β-cell-specific CD8 and CD4 T cell differentiation and function, the role of autoimmune stem-like progenitor CD8 T cells in initiating and sustaining disease, and molecular programs and key transcription factors associated with the diabetogenic T cell response.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390344","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
Type 1 Diabetes: Advances in Understanding and Treatment 100 Years after the Discovery of Insulin. 1型糖尿病:胰岛素发现100年后的认识和治疗进展。
IF 10.1 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2026-05-01 DOI: 10.1101/cshperspect.a041843
Jeffrey A Bluestone, Kevan C Herold, Lori Sussel
{"title":"Type 1 Diabetes: Advances in Understanding and Treatment 100 Years after the Discovery of Insulin.","authors":"Jeffrey A Bluestone, Kevan C Herold, Lori Sussel","doi":"10.1101/cshperspect.a041843","DOIUrl":"10.1101/cshperspect.a041843","url":null,"abstract":"<p><p>Type 1 diabetes is an autoimmune condition in which the pancreatic β cells that produce insulin are destroyed by the body's immune system. For 100 years, diet and insulin injections have been the only effective treatment. Recent advances have led to significant progress in our understanding of the pathogenesis of the disease and the interplay between the environment, components of the immune system, and the β cells that are targeted. This has led to new therapies that rebalance the immune system and finally offer the promise of a cure.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390347","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
Pediatric Tuberculosis: Epidemiology, Disease Spectrum, Diagnosis, and Management. 儿童结核病:流行病学、疾病谱系、诊断和管理。
IF 10.1 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2026-05-01 DOI: 10.1101/cshperspect.a041805
Ben J Marais, H Simon Schaaf
{"title":"Pediatric Tuberculosis: Epidemiology, Disease Spectrum, Diagnosis, and Management.","authors":"Ben J Marais, H Simon Schaaf","doi":"10.1101/cshperspect.a041805","DOIUrl":"10.1101/cshperspect.a041805","url":null,"abstract":"<p><p>Tuberculosis (TB) is a major cause of disease and death in young children from TB-endemic countries, especially in areas affected by poverty, social disruption, and human immunodeficiency virus (HIV) infection. This article reviews the disease burden and the natural history of disease in children with TB. It also provides guidance regarding the diagnosis, treatment, and prevention of TB in children.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437339","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
The Mouse Model of Tuberculosis: Uses and Abuses. 结核小鼠模型:应用与滥用。
IF 10.1 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2026-04-27 DOI: 10.1101/cshperspect.a041820
Andrea M Cooper, John E Pearl
{"title":"The Mouse Model of Tuberculosis: Uses and Abuses.","authors":"Andrea M Cooper, John E Pearl","doi":"10.1101/cshperspect.a041820","DOIUrl":"https://doi.org/10.1101/cshperspect.a041820","url":null,"abstract":"<p><p>The mouse provides a flexible tool to probe the interactions between the immune system and the slow growing and persistent bacterium, <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>). Removal of specific cells or molecules from mice demonstrates the causal connection between these elements and control of <i>Mtb</i>; these connections are also seen in humans. Systems genetics, with single-cell and spatial technologies, have transformed the working model of immunity to tuberculosis (TB) in mice and humans; determining the spatiotemporal role of immune elements in immunity will allow development of targeted and precise interventions to control TB. As cure from TB is associated with lifelong health consequences, we need to also use mouse models to understand the health impact of the immune response to TB. Use of the mouse model requires precise experimental design and cautious interpretation. Rational incorporation of mouse-derived data into our working model of TB will refine our understanding of the natural history of TB worldwide.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764728","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
From Empirical Discovery to Targeted Therapy: The Evolution of Tuberculosis Treatment. 从经验发现到靶向治疗:结核病治疗的演变。
IF 10.1 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2026-04-27 DOI: 10.1101/cshperspect.a041821
Natalie J E Waller, Kyu Y Rhee
{"title":"From Empirical Discovery to Targeted Therapy: The Evolution of Tuberculosis Treatment.","authors":"Natalie J E Waller, Kyu Y Rhee","doi":"10.1101/cshperspect.a041821","DOIUrl":"https://doi.org/10.1101/cshperspect.a041821","url":null,"abstract":"<p><p>Tuberculosis (TB) chemotherapy was once considered a crowning triumph of modern medicine but has since reemerged as a persisting paradox. While therapeutically still effective in most cases, current frontline treatments for TB remain largely unchanged from their introduction over 50 years ago and continue to require a minimum of 6 months of multidrug treatment to achieve durable cure, limiting both their individual and population level impact. Its impact has been further eroded by the emergence and spread of drug resistance. Although new antibiotics active against drug-resistant TB are beginning to emerge, their integration into shorter, more effective regimens has proven difficult. This review revisits the evolution of TB chemotherapy and explores how individual drug properties shape overall regimen efficacy and treatment duration. While initially shaped by efforts to prevent resistance-based treatment failures while minimizing toxicity, the empirical development of combination chemotherapies revealed additional determinants of treatment efficacy that extended beyond conventional antimicrobial potency and impacted treatment duration. By integrating classical findings with modern insights into pharmacology, lesion physiology, and bacterial persistence, we highlight the potential that mechanism-based insights into existing TB chemotherapies could guide the rational design of next-generation, treatment-shortening combinations.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764751","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
The Global Epidemiology of Tuberculosis: Burden, Trends, and Determinants. 全球结核病流行病学:负担、趋势和决定因素。
IF 10.1 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2026-04-27 DOI: 10.1101/cshperspect.a041982
Gerhard Walzl, Delia Goletti, Alimuddin Zumla
{"title":"The Global Epidemiology of Tuberculosis: Burden, Trends, and Determinants.","authors":"Gerhard Walzl, Delia Goletti, Alimuddin Zumla","doi":"10.1101/cshperspect.a041982","DOIUrl":"https://doi.org/10.1101/cshperspect.a041982","url":null,"abstract":"<p><p>Tuberculosis (TB) remains the leading cause of death from an infectious disease worldwide despite availability of effective treatment. In 2024, an estimated 10.7 million people developed TB disease, including 5.8 million men, 3.7 million women, and 1.2 million children. An estimated 1.23 million people died of TB, including 150,000 deaths among people living with human immunodeficiency virus (HIV). TB occurs in all regions of the world but is highly concentrated in a number of countries and populations, reflecting persistent social, economic, and health-system inequalities. Approximately one-fifth of the world's population has TB infection. TB burden varies markedly by age, sex, geography, and risk profile. TB/HIV coinfection remains a major driver of TB mortality, particularly in sub-Saharan Africa. Children and adolescents account for a substantial and underrecognized share of the global burden. Drug-resistant TB remains a major threat, driven by ongoing transmission and gaps in access to timely diagnosis and effective treatment. Global TB incidence declined between 2000 and 2019 but stalled during the COVID-19 pandemic. Case detection and mortality have partially recovered since 2022. Currently, 131 cases per 100,000 population and funding cuts highlight the fragility of TB control efforts. Sustained reductions in TB burden and achieving WHO End TB goals will require strong political and funder commitments in early diagnosis, expanded prevention, universal access to effective treatment for all forms of TB, strengthened surveillance, and action on the social and structural determinants that drive transmission and disease.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764742","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
Diagnostic Assays for TB Disease and Drug Resistance Detection-Advances and Latest WHO Recommendations. 结核病诊断分析和耐药性检测——进展和世卫组织最新建议。
IF 10.1 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2026-04-27 DOI: 10.1101/cshperspect.a041850
Paolo Miotto, Francesca Saluzzo, Andrea M Cabibbe, Daniela M Cirillo
{"title":"Diagnostic Assays for TB Disease and Drug Resistance Detection-Advances and Latest WHO Recommendations.","authors":"Paolo Miotto, Francesca Saluzzo, Andrea M Cabibbe, Daniela M Cirillo","doi":"10.1101/cshperspect.a041850","DOIUrl":"https://doi.org/10.1101/cshperspect.a041850","url":null,"abstract":"<p><p>Accurate and timely diagnosis of active tuberculosis (TB) and its drug-resistant forms are essential for effective patient care and global TB disease control. This paper summarizes the latest advances in TB disease diagnostics. We describe mechanisms of drug resistance in <i>Mycobacterium tuberculosis</i>, including both well-characterized and emerging pathways. Approaches for the initial detection of active TB disease are discussed, highlighting the key role of nucleic acid amplification tests of varying complexity across pulmonary and extrapulmonary specimens. Follow-on drug resistance testing using rapid molecular assays and next-generation sequencing (NGS) enables the early identification of resistance to first- and second-line drugs. Traditional culture-based and phenotypic drug susceptibility testing remain crucial for comprehensive profiling, particularly for drugs with limited molecular markers. These topics are discussed in the context of World Health Organization (WHO) recommendations. We also outline future directions, emphasizing the integration of molecular and phenotypic methods, expansion of NGS applications, and standardization of diagnostic algorithms. This synthesis provides a concise overview of contemporary diagnostic tools to guide therapy and policy decisions in TB disease management.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764704","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
Immunodominant Tuberculosis Antigens Recognized by Human CD4+ and CD8+ T Cells. 人类CD4+和CD8+ T细胞识别的免疫优势结核抗原。
IF 10.1 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2026-04-17 DOI: 10.1101/cshperspect.a041816
Deborah A Lewinsohn, Cecilia S Lindestam Arlehamn, Alessandro Sette, David M Lewinsohn
{"title":"Immunodominant Tuberculosis Antigens Recognized by Human CD4<sup>+</sup> and CD8<sup>+</sup> T Cells.","authors":"Deborah A Lewinsohn, Cecilia S Lindestam Arlehamn, Alessandro Sette, David M Lewinsohn","doi":"10.1101/cshperspect.a041816","DOIUrl":"https://doi.org/10.1101/cshperspect.a041816","url":null,"abstract":"<p><p>Tuberculosis (TB), caused by infection with <i>Mycobacterium tuberculosis</i> (MTB), represents an important cause of morbidity and mortality worldwide for which an improved vaccine and immunodiagnostics are urgently needed. CD4<sup>+</sup> and CD8<sup>+</sup> T cells play an important role in host defense to TB. Definition of the immunodominant antigens recognized by these T cells is critical for improved understanding of the immunobiology of TB and for development of vaccines and diagnostics. Herein, we review antigens and epitopes recognized by classically human leukocyte antigen (HLA) class I- and class II-restricted CD4<sup>+</sup> and CD8<sup>+</sup> T cells in humans infected with MTB, as defined using either targeted or genome-wide approaches. We address the extent to which these antigens have been defined as immunodominant, protective, and/or specific to disease stages in humans and, with particular relevance to CD8<sup>+</sup> T-cell recognition, whether these antigens are displayed by MTB-infected cells.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715900","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
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