Immunology最新文献

{"title":"Cytotoxic Signature and IFN-γ Production Dominate CD4⁺ T-Cell Response During Human Toxoplasmosis.","authors":"Priscilla Miranda Henriques, Gregório Guilherme Almeida, Inga Rimkute, Luara Isabela Dos Santos, Thomas Liechti, Ana Paula Marino, Isabela Natália Pascoal Campos do Vale, Daniel Vitor Vasconcelos-Santos, Olindo Assis Martins-Filho, Ricardo Tostes Gazzinelli, Mario Roederer, Alan Sher, Andréa Teixeira-Carvalho, Dragana Jankovic, Lis Ribeiro do Valle Antonelli","doi":"10.1111/imm.13912","DOIUrl":"https://doi.org/10.1111/imm.13912","url":null,"abstract":"<p><p>Toxoplasma gondii is a highly versatile parasite that infects most warm-blooded animals and is a major cause of retinochoroiditis and uveitis in humans. The pathophysiology of these conditions remains poorly understood. Both parasite virulence and host inflammatory response contribute to the development of ocular disease. While CD4⁺ T cells play a critical role in host resistance to Toxoplasma infection, their kinetics and effector functions, as well as their contribution to the clinical outcome of the infection, including ocular involvement, remain poorly understood. To address this question, we investigated the immune response during acute and convalescent toxoplasmosis and stratified patients further based on the presence or absence of ocular disease. We found that T. gondii infection leads to decreased and increased proportions of central and effector memory CD4⁺ T cells, respectively. Applying unsupervised analysis, distinct CD4⁺ T-cell subsets were determined. Among 50 clusters, 10 produced cytotoxic proteins (granzyme B and perforin) and one produced cytokines upon antigen-specific stimulation. We observed that proportions of five CD4⁺ T-cell clusters out of 50 were different during acute disease between T. gondii-infected patients with and without ocular lesions. Interestingly, three of the five displayed a cytotoxic signature indicating their possible involvement in ocular immunopathology. Taken together, our results reveal that during T. gondii infection, CD4⁺ T cells not only develop a Th1 cytokine profile, but also acquire previously unappreciated cytotoxic capacity/function. These results, while underscoring the complexity of the CD4⁺ T-cell response to T. gondii, suggest that specific subsets may be involved in the development of pathology and provide possible targets for therapeutic intervention.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ammonia-Induced Cell Death: A Novel Frontier to Enhance Cancer Immunotherapy.","authors":"Urushi Rehman, Garima Gupta, Amirhossein Sahebkar, Prashant Kesharwani","doi":"10.1111/imm.13918","DOIUrl":"https://doi.org/10.1111/imm.13918","url":null,"abstract":"<p><p>Cancer immunotherapy has revolutionized treatment paradigms, but its efficacy is often curtailed by T-cell exhaustion and the suppressive tumour microenvironment. Recent studies reveal a novel mechanism of T-cell demise termed ammonia-induced cell death (AICD), which significantly impacts effector CD8+ T-cell survival and function. This phenomenon arises from metabolic reprogramming during immune activation, wherein heightened glutamine metabolism leads to the accumulation of toxic ammonia levels. Ammonia damages lysosomes and mitochondria, disrupting cell balance and causing apoptosis. These insights provide a unique metabolic perspective on T-cell attrition, underscoring the critical interplay between metabolic byproducts and immune regulation. Targeting AICD offers promising therapeutic avenues to bolster immunotherapy. Strategies such as inhibiting ammonia transport, enhancing autophagic pathways and employing ammonia scavengers may extend T-cell longevity and improve antitumor efficacy. Moreover, integrating ammonia modulation with established immunotherapies, including immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy, could yield synergistic benefits. Addressing this metabolic bottleneck is particularly compelling in immune 'cold' tumours resistant to conventional therapies. However, further research is essential to refine these interventions, evaluate safety profiles and explore broader applications across cancer types. Ammonia metabolism thus represents a transformative frontier in advancing cancer immunotherapy and precision oncology.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful Treatment of Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) With Tezepelumab: A Case Report.","authors":"Mattia Cristallo, Mirco Filieri, Federico Spataro, Loredana Muolo, Eustachio Nettis, Attilio Di Girolamo","doi":"10.1111/imm.13915","DOIUrl":"https://doi.org/10.1111/imm.13915","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Significance of Metagenomic Next-Generation Sequencing in Immunocompromised Patients With Suspected Pulmonary Infection.","authors":"Xi Zheng, Wei Zou, Shumei Zou, Jia Ye, Zhenming Bao, Yingfang Song","doi":"10.1111/imm.13911","DOIUrl":"https://doi.org/10.1111/imm.13911","url":null,"abstract":"<p><p>Immunocompromised hosts are highly vulnerable to lung infections, but the efficacy of traditional diagnosis is unsatisfactory. Metagenomic next-generation sequencing (mNGS) has high throughput and broad coverage. Its value in different types of immunocompromised patients has yet to be fully explored. Therefore, the study aims to evaluate the value of mNGS in immunocompromised patients. Clinical data from immunocompromised patients with suspected pulmonary infection (PI) (September 2018-2021) were retrospectively analysed. Patients were categorised into PI (87 cases) and non-pulmonary infection (NPI, 14 cases) groups. The diagnostic performance between mNGS and conventional microbiological tests (CMTs) was compared. Subgroup analyses were also conducted based on whether the patients received organ transplantation, including the comparison of the diagnostic performance of mNGS and culture and the spectrum of characteristics among them. mNGS demonstrated significantly elevated diagnostic sensitivity (p < 0.001) over traditional methods, with a pronounced advantage in identifying mixed PIs (p < 0.05). Among immunocompromised cohorts, mNGS outperformed cultures, showing higher positivity rates in both organ transplant (p < 0.001) and non-transplant patients (p < 0.001). Mixed infections, predominantly bacterial-fungal, were more prevalent in transplant recipients with reduced lymphocytes and CD4⁺ T cells. Pathogen profiles differed, with Pneumocystis jirovecii, Cytomegalovirus, and Pseudomonas aeruginosa predominating in organ transplant recipients, and P. jirovecii, P. aeruginosa, Streptococcus pneumoniae and Streptococcus pallidum in non-transplant individuals. mNGS is valuable in diagnosing PI and mixed infections in immunocompromised patients, which may be particularly suitable for identifying mixed infections in patients with organ transplants and low lymphocyte and CD4⁺ T lymphocyte counts.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of HMC3 and C20 Microglial Cell Lines Reveals Differential Myeloid Characteristics and Responses to Immune Stimuli.","authors":"Bavani Gunasegaran, Shivani Krishnamurthy, Sharron S Chow, Millijoy D Villanueva, Anna Guller, Seong Beom Ahn, Benjamin Heng","doi":"10.1111/imm.13900","DOIUrl":"https://doi.org/10.1111/imm.13900","url":null,"abstract":"<p><p>Microglia are the primary resident immune cells of the central nervous system (CNS) that respond to injury and infections. Being critical to CNS homeostasis, microglia also have been shown to contribute to neurodegenerative diseases and brain cancer. Hence, microglia are regarded as a potential therapeutic target in CNS diseases, resulting in an increased demand for reliable in vitro models. Two human microglia cell lines (HMC3 and C20) are being used in multiple in vitro studies, however, the knowledge of their biological and immunological characteristics remains limited. Our aim was to identify and compare the biological changes in these immortalised immune cells under normal physiological and immunologically challenged conditions. Using high-resolution quantitative mass spectrometry, we have examined in-depth proteomic profiles of non-stimulated and LPS or IFN-γ challenged HMC3 and C20 cells. Our findings reveal that HMC3 cells responded to both treatments through upregulation of immune, metabolic, and antiviral pathways, while C20 cells showed a response associated with mitochondrial and immune activities. Additionally, the secretome analysis demonstrated that both cell lines release IL-6 in response to LPS, while IFN-γ treatment resulted in altered kynurenine pathway activity, highlighting distinct immune and metabolic adaptations.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lineage Tracking Dissects the Fate of Neonatal iNKT Cells Later in Life.","authors":"Jun Liu, Biao Yang, Danchen Hu, Ning Yuan, Wenhua Li, Zhao Feng, Yanhong Su, Dan Zhang, Xiaofeng Yang, Baojun Zhang","doi":"10.1111/imm.13909","DOIUrl":"https://doi.org/10.1111/imm.13909","url":null,"abstract":"<p><p>Invariant natural killer T (iNKT) cells in peripheral tissues are from different waves ranged from foetal, neonatal to adult ages. However, it is unclear how iNKT cells from different ages maintain in the periphery and what are their functionality. We found that in adult mice, neonate tracked-iNKT (NT-iNKT) cells are present in spleen, bone marrow, liver and lung, with a predominantly accumulation in the kidney. The NT-iNKT cells in the kidney are almost iNKT1 cells and express tissue-resident marker CD69. These cells also exhibit higher level of CD122 and possess a stronger proliferative capacity compared to adult tracked-iNKT (AT-iNKT) cells. Furthermore, we found that NT-iNKT cells potentially secrete more IFN-γ than AT-iNKT cells in vitro and in vivo (a-GalCer immunisation). Overall, our study sheds light on the peripheral behaviour and functionality of NT- and AT-iNKT cells, highlighting the potential role of NT-iNKT cells in the kidney during immune response.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icariin Induces Chondrocyte Degeneration via Activation of the NF-κB Signalling Pathway and Reduces the Inflammation Factor Expression Induced by Lipopolysaccharide.","authors":"Tianjun Zhai, Jie Wang, Yeping Chen, Jianqing Su, Wei Feng","doi":"10.1111/imm.13906","DOIUrl":"https://doi.org/10.1111/imm.13906","url":null,"abstract":"<p><p>To investigate the effect of icariin on chondrocytes by activating the nuclear factor kappa-B (NF-κB) signalling pathway and the mechanism of icariin in inducing chondrocytes degeneration. Chondrocytes were cultured in vitro and treated with icariin at concentrations of 0, 0.01, 0.1, 10 and 20 μm. Cell proliferation was evaluated by cell counting kit-8 (CCK8) method, apoptosis was detected by TUNEL method and the expression of NF-κB was detected by Western blotting (WB) and RT-PCR. The nuclear localization of NF-κB p65 protein was observed by immunofluorescence staining. Lipopolysaccharide (LPS) was used to establish the inflammatory model, and WB and RT-PCR were used to detect the expression levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6). After treatment with icariin, the proliferation ability of chondrocytes was markedly enhanced, and the apoptosis rate (AR) was markedly decreased (p < 0.05). In addition, icariin could inhibit the nuclear translocation of NF-κB p65 protein, promote the gene expression of Collagen II (Col-II) and Aggrecan in chondrocytes, and reduce the expression of NF-κB. Moreover, icariin markedly reduced the expression of IL-6 and TNF-α in LPS-induced inflammation (p < 0.05). Icariin can enhance chondrocyte proliferation, promote phenotypic gene expression by inhibiting the NF-κB signal transduction pathways, thus suppressing the chondrocyte degeneration, and can reduce the inflammation factor expression induced by LPS.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Carriage of Prevotella copri Is Associated With Increased Thymus Derived Naïve Regulatory T Cells in Cord Blood","authors":"Yuan Gao,&nbsp;Martin O'Hely,&nbsp;Fiona Collier,&nbsp;Anne-Louise Ponsonby,&nbsp;Mimi L. K. Tang,&nbsp;John Molloy,&nbsp;Peter Vuillermin,&nbsp;the BIS Investigator Group","doi":"10.1111/imm.13904","DOIUrl":"10.1111/imm.13904","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"174 4","pages":"481-484"},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Pre-Infection COVID-19 Vaccination on the Incidence and Severity of Long COVID: A Retrospective Case-Control Study.","authors":"Elena Barado, Silvia Carlos, Laura Moreno-Galarraga, Fares Amer, Nicolás Escrivá, María Gabriela Torres, Gabriel Reina, Alejandro Fernandez-Montero","doi":"10.1111/imm.13908","DOIUrl":"https://doi.org/10.1111/imm.13908","url":null,"abstract":"<p><p>Long COVID is an emerging condition with an important impact on the quality of life of affected individuals. This study aims to analyse the association between complete vaccination prior to SARS-CoV-2 infection and the subsequent development of long COVID, including its symptoms and their frequency through a retrospective case-control study. Cases included participants with long COVID, while controls were participants without long COVID but who had a SARS-CoV-2 infection. Data were collected through a self-reported survey. The study demonstrates a significant association between vaccination and a lower incidence of long COVID, adjusted for sex, age, university education, body mass index, physical activity, race, tobacco use, alcohol intake, adherence to Mediterranean diet, previous illness, flu vaccination, health care worker, high-risk COVID worker and sleep hours and sedentarism (OR 0.49, CI 95% 0.28-0.87). Furthermore, there is a statistically significant association between vaccination and reduced symptoms such as anosmia, dysgeusia, myalgia or arthralgia, as well as a lower overall number, adjusted for the aforementioned variables. These findings suggest that the vaccine could be associated not only to a milder course of SARS-CoV-2 infection but also with an improvement in the state of long COVID and its symptoms.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"X-Ray Crystallography Based Epitope Mapping of Glycoproteins and RNA in Chandipura Vesiculovirus for Vaccine Design.","authors":"Aron Rodrick Lakra","doi":"10.1111/imm.13907","DOIUrl":"https://doi.org/10.1111/imm.13907","url":null,"abstract":"<p><p>This study investigates potential epitopes in the glycoprotein and RNA of Chandipura vesiculovirus (CHPV) using MHC Class I (HLA-A0201) and MHC Class II (DRB1_0101) molecules with 3D structures derived from x-ray crystallography. Computationally derived peptides were mapped and subjected to in silico docking, revealing promising targets for CD8+ cytotoxic and CD4+ helper T cells. Key factors analysed include solvent accessible surface area (SASA), Debye-Waller factor (B-factor), and polar bond interactions. Post-docking, removal of N-acetylglucosamine (NAG) increased peptide stability and reduced B-factors, while SO4 presence had minimal impact. SASA values increased by up to 237.5% with MHC Class I, and RNA docking with MHC Class II displayed mixed SASA changes. Polar bond interactions also increased post-docking, indicating the strong potential of identified CHPV epitopes.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}