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Ascaris Lumbricoides Cystatin Impairs IL-1β Maturation and CD14 Expression in Human Monocytes. 蛔虫半胱抑素对人单核细胞IL-1β成熟和CD14表达的影响
IF 4.9 3区 医学
Immunology Pub Date : 2025-07-08 DOI: 10.1111/imm.70016
Ana Lozano, Josefina Zakzuk, Nathalie Acevedo, Andrew R Williams, Luis Caraballo
{"title":"Ascaris Lumbricoides Cystatin Impairs IL-1β Maturation and CD14 Expression in Human Monocytes.","authors":"Ana Lozano, Josefina Zakzuk, Nathalie Acevedo, Andrew R Williams, Luis Caraballo","doi":"10.1111/imm.70016","DOIUrl":"https://doi.org/10.1111/imm.70016","url":null,"abstract":"<p><p>Ascaris lumbricoides cystatin (Al-CPI), a cysteine protease inhibitor, has shown anti-inflammatory effects in models of house dust mite-induced respiratory allergy and experimental colitis. Since monocytes are primary targets of cystatins, and helminth-derived products can induce immunoregulatory monocytes that mitigate autoimmune and inflammatory diseases in murine models, we aimed to investigate the immunoregulatory effects of Al-CPI on human monocytes and its mechanisms. Monocytes were isolated from healthy donors using CD14+ magnetic beads and treated with recombinant Al-CPI (rAl-CPI) before activation with LPS. Surface marker expression and caspase-1 activity were analysed by flow cytometry, while cytokine levels were quantified using bead-based assays. Caspase-8 inhibition was measured by fluorescence, and pro-IL-1β expression was evaluated by Western blot. RNA-seq and differential gene expression analyses were performed using DESeq2 and GSEA. rAl-CPI reduced cell surface expression of HLA-DR and CD14 as well as IL-1β levels in cell culture supernatants. Transcriptomic analysis identified 30 differentially expressed genes (12 upregulated and 18 downregulated; padj < 0.05 and fold change [FC] < |1.5|), including the downregulation of CD14 and SLAMF1, both involved in LPS-mediated signalling through the TLR4-TRIF pathway. GSEA analysis showed that rAl-CPI plus LPS induced an enrichment of the IFN signalling pathway compared with LPS (NES = 1.88; padj < 0.0001). Further analysis of IL-1β production and maturation showed that rAl-CPI did not alter pro-IL-1β levels, but reduced caspase-1 activation. In conclusion, rAl-CPI may impair IL-1β maturation and release by modulating the alternative inflammasome activation, potentially through downregulation of CD14 and other key regulatory molecules involved in this pathway.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583822","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}
引用次数: 0
The Role and Mechanism of Anti-ICOS mAb in Experimental Autoimmune Encephalomyelitis. 抗icos单抗在实验性自身免疫性脑脊髓炎中的作用及机制
IF 4.9 3区 医学
Immunology Pub Date : 2025-06-30 DOI: 10.1111/imm.70014
Minjun Xiao, Yun Zhao, Xue Zhang, Qi Sun, Ge Gao, Nan Wu, Xueli Fan
{"title":"The Role and Mechanism of Anti-ICOS mAb in Experimental Autoimmune Encephalomyelitis.","authors":"Minjun Xiao, Yun Zhao, Xue Zhang, Qi Sun, Ge Gao, Nan Wu, Xueli Fan","doi":"10.1111/imm.70014","DOIUrl":"https://doi.org/10.1111/imm.70014","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Targeting costimulatory signalling pathways, especially inducible T-cell costimulatory (ICOS)-ICOS ligand(ICOSL) co-stimulatory signal, has been widely used as a therapeutic target in autoimmune diseases. Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating and neurodegenerative disease in the central nervous system. At present, few studies are addressing the role of the ICOS-ICOSL co-stimulatory pathway in MS. We aimed to explore the role of anti-ICOS mAb in the immune response of EAE and further reveal the regulatory mechanism. C57BL/6 female mice (6-8 weeks old, 18-20 g) were randomly divided into EAE group, T1 group, T9 group and T30 group. The EAE model was established in the three groups by MOG active immunisation. Symptom scores and weights of mice were recorded every day after modelling. Mice in the T1 and the T9 groups were given intraperitoneal injections of anti-ICOS mAb on Day 1 or 9 after active immunisation, respectively. Anti-ICOS mAb were injected three times total, each injection separated by 72 h. On the 19th day after modelling, the mice were sacrificed and the spinal cord tissues of each group were collected. Mice in the T30 group were given an intraperitoneal injection of anti-ICOS mAb on Day 9 after active immunisation. These anti-ICOS mAb were injected continuously until Day 30. On Day 30 after the establishment of the model, the mice were sacrificed and spinal cord tissues were collected. HE staining was used to observe the inflammatory infiltration of the spinal cord in each group of mice. Transcriptome sequencing was used to detect gene transcription in spinal cord tissues of mice and to explore the signalling pathways that might be involved. Finally, the signalling pathway was verified by Western blot. (1) Compared with the EAE group, there are significantly lower behavioural scores, heavier weight, delayed onset time and fewer inflammatory infiltrations of the spinal cord in the T9 group and T30 group. However, there were no significant differences in behavioural scores, weight, onset time and inflammatory infiltration between the EAE group and the T1 group. (2) The R&lt;sup&gt;2&lt;/sup&gt; value of the spinal cord sample in each group was greater than 0.8. There were 6569 differentially expressed genes (DEGs) between T9 group and EAE group, including 2579 up-regulated genes and 3990 down-regulated genes. There were 487 DEGs between T1 and EAE groups, including 131 up-regulated genes and 356 down-regulated genes. There were 7116 DEGs between T9 and T1 groups, including 2921 up-regulated genes and 4195 down-regulated genes. KEGG enrichment showed that DEGs between T9 group and EAE group were mainly enriched in Epstein-Barr virus infection, NF-κB signalling pathway, FcγR-mediated phagocytosis, natural killer cell-mediated cytotoxicity, as well as Th17, Th1 and Th2 cell differentiation pathways. In the most significantly enriched EB pathway, we found that the fold change of key genes SYK, PI3K and AKT was -4.345","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527763","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}
引用次数: 0
Distinct T Cell Receptor Clonotypes in the Sardinian Population Highlight the Role of Mucosal-Associated Invariant T Cells and Invariant Natural Killer T Cells in Multiple Sclerosis. 撒丁岛人群中不同的T细胞受体克隆型强调了粘膜相关不变T细胞和不变自然杀伤T细胞在多发性硬化症中的作用。
IF 4.9 3区 医学
Immunology Pub Date : 2025-06-29 DOI: 10.1111/imm.70013
Jiaxin Shen, Elena Rita Simula, Yisu Liu, Gustavo Sganzerla Martinez, Xiaofen Wen, David J Kelvin, Leonardo A Sechi
{"title":"Distinct T Cell Receptor Clonotypes in the Sardinian Population Highlight the Role of Mucosal-Associated Invariant T Cells and Invariant Natural Killer T Cells in Multiple Sclerosis.","authors":"Jiaxin Shen, Elena Rita Simula, Yisu Liu, Gustavo Sganzerla Martinez, Xiaofen Wen, David J Kelvin, Leonardo A Sechi","doi":"10.1111/imm.70013","DOIUrl":"https://doi.org/10.1111/imm.70013","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory disease of the central nervous system, driven by T-cell mediated immune responses. Studying T-cell receptor (TCR) clonotypes specific to MS in distinct populations can provide insights into disease mechanisms. The Sardinian population, with its unique genetic background resulting from geographical isolation, presents a high-risk cohort for MS research, offering a valuable context for understanding the disease's pathogenesis. We analysed the frequency of unique TCR clonotypes in peripheral blood samples from Sardinian MS patients and healthy controls, focusing on TCRα and TCRβ CDR3 sequences. Clonotypes were functionally annotated for antigen-specific interactions, and hierarchical analysis was performed to identify shared TCR clonotypes between MS patients and healthy controls. A total of 119 TCRβ and 521 TCRα CDR3 clonotypes were significantly more frequent in MS patients compared to healthy controls (p < 0.05). Several TCR-α clonotypes, such as CAVLDSNYQLIW (a MAIT cell clonotype targeting the BST2 antigen) and CAVNTGNQFYF (cross-reactive to multiple antigens, including CMV p65 and BST2), were identified as specific to MS. Shared clonotype analysis revealed the involvement of mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cells in MS pathogenesis. Notably, HCV-specific TCR-α clonotypes (NS3-HCV) were significantly increased in MS patients, suggesting a link between infectious disease-related and autoimmune-related clonotypes. No significant differences were observed for other antigens, such as VP22, p65 and BST2. This study identifies distinct TCR clonotypes associated with MS in the Sardinian population, highlighting the role of MAIT and iNKT cells in the disease's pathogenesis. The findings suggest that HCV-specific TCR repertoires may contribute to the development of MS. These results improve our understanding of T-cell mediated immune mechanisms in MS and offer potential targets for therapeutic intervention, particularly within the Sardinian cohort.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527762","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}
引用次数: 0
CD73 Expression by CD4+ T Cells Marks Early Effector Memory T Cells. CD4+ T细胞表达CD73标志早期效应记忆T细胞。
IF 4.9 3区 医学
Immunology Pub Date : 2025-06-26 DOI: 10.1111/imm.70011
Luxia Chen, Sabine Ring, Anna Jurga, Florian C Kurschus, Alexander Enk, Karsten Mahnke
{"title":"CD73 Expression by CD4<sup>+</sup> T Cells Marks Early Effector Memory T Cells.","authors":"Luxia Chen, Sabine Ring, Anna Jurga, Florian C Kurschus, Alexander Enk, Karsten Mahnke","doi":"10.1111/imm.70011","DOIUrl":"https://doi.org/10.1111/imm.70011","url":null,"abstract":"<p><p>CD73 is a membrane bound ectoenzyme, dephosphorylating adenosine mono- and di-phosphate to immunosuppressive adenosine. It is strongly expressed by CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells, but when analysing conventional CD4<sup>+</sup> T cells only 50% express CD73. When analysing these two clearly distinct (i.e., CD73<sup>+</sup> and CD73<sup>-</sup>) populations, we found that the naïve CD73<sup>+</sup>CD4<sup>+</sup> subset exerted superior proliferation over the CD73<sup>-</sup>CD4<sup>+</sup> cells, was more resistant to activation induced cells death (AICD) and was prone to develop into a \"Th1-like\" cell type, expressing the prototypic cytokines (IFN-γ, TNF-α) and specific transcription factors (i.e., Tbx21). Upon transfer into lymphopenic hosts, CD73<sup>+</sup>CD4<sup>+</sup> cells exhibited increased proliferation and survival, and accumulated in inflammatory tissues, developing a CD44<sup>+</sup>CD62L<sup>-</sup> effector memory phenotype. Therefore, we conclude that CD73 in naïve CD4<sup>+</sup> T cells functions as a promotor of survival and proliferation of T cells, as well as a marker for their further differentiation into effector T cells.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505578","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}
引用次数: 0
Radiofrequency Ablation and Immunotherapy: Orchestrating the Immune Microenvironment for Improved Hepatocellular Carcinoma Control 射频消融和免疫治疗:协调免疫微环境改善肝细胞癌的控制。
IF 5 3区 医学
Immunology Pub Date : 2025-06-26 DOI: 10.1111/imm.70004
Liu Yang, Shuhang Wei, Zongxin Liu, Qiqi Liu, Zhen Yu, Yuemin Feng, Qiang Zhu
{"title":"Radiofrequency Ablation and Immunotherapy: Orchestrating the Immune Microenvironment for Improved Hepatocellular Carcinoma Control","authors":"Liu Yang,&nbsp;Shuhang Wei,&nbsp;Zongxin Liu,&nbsp;Qiqi Liu,&nbsp;Zhen Yu,&nbsp;Yuemin Feng,&nbsp;Qiang Zhu","doi":"10.1111/imm.70004","DOIUrl":"10.1111/imm.70004","url":null,"abstract":"<p>Radiofrequency ablation (RFA) is a radical treatment modality for early-stage hepatocellular carcinoma (HCC). In addition to directly eliminating tumour cells, RFA induces changes in infiltrating cells within the liver tumour immune microenvironment (TIME), thereby eliciting anti-tumour immune effects. Moreover, incomplete radiofrequency ablation (IRFA) induces an immunosuppressive tumour microenvironment, which inhibits anti-tumour immune responses and promotes tumour recurrence and metastasis. Immunotherapy, a systemic treatment, activates or enhances the immune system to recognise and eliminate tumour cells. Thus, orchestrating the TIME makes it possible to combine RFA and immunotherapy, which may significantly enhance the anti-tumour immune response to target residual tumour cells. This combinatorial approach may emerge as a pivotal strategy to augment HCC control and mitigate post-RFA recurrence. This review discusses how RFA modulates the TIME in HCC, and the immune-related mechanisms leading to tumour cell survival and invasion after IRFA. Finally, we summarise the combined mechanisms of the two modalities on TIME, and their clinical implications for treating HCC, aiming to provide new insights for the combined strategy of RFA and immunotherapy.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 3","pages":"322-336"},"PeriodicalIF":5.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
γδT Cells in IBD: Beneficial or Detrimental? γδT细胞在IBD中的作用:有益还是有害?
IF 5 3区 医学
Immunology Pub Date : 2025-06-25 DOI: 10.1111/imm.70012
Baoqing Xu, Jianbin Ji, Lingling Ma, Chunyan Wang, Lianjing Pang, QingChao Song, Yang Liu, Zhenghua Zhou, Fanfan Qu
{"title":"γδT Cells in IBD: Beneficial or Detrimental?","authors":"Baoqing Xu,&nbsp;Jianbin Ji,&nbsp;Lingling Ma,&nbsp;Chunyan Wang,&nbsp;Lianjing Pang,&nbsp;QingChao Song,&nbsp;Yang Liu,&nbsp;Zhenghua Zhou,&nbsp;Fanfan Qu","doi":"10.1111/imm.70012","DOIUrl":"10.1111/imm.70012","url":null,"abstract":"<p>γδT cells play a crucial role in inflammatory bowel disease (IBD). Studies have shown that the number, subsets and secreted cytokines of γδT cells undergo changes in IBD. However, whether γδT cells are beneficial or detrimental in IBD remains controversial. Some studies suggest that γδT cells have a protective role in colitis, while others indicate that the expansion and activation of γδT cells may exacerbate colitis. Several studies have explored γδT cell-based therapies for immune disorders, and γδT cell-based therapy for IBD has emerged as a promising research direction. There are numerous reviews of γδT cells and autoimmune diseases, but few reviews focus on γδT and IBD. Therefore, this article briefly summarises the current understanding of γδT cells in IBD.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 3","pages":"337-348"},"PeriodicalIF":5.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Palmitoylethanolamide (PEA) Induces an Increase in Spleen Regulatory T Cells, Reduces CD8 + Cells and TNF-α Levels in Target Organs, and Protects Mice From Graft-Versus-Host Disease-Related Mortality Through PPAR Activation Without Compromising the Graft-Versus-Tumour Response 棕榈酰乙醇酰胺(PEA)诱导脾脏调节性T细胞增加,降低靶器官中CD8+细胞和TNF-α水平,并通过PPAR激活保护小鼠免于移植物抗宿主病相关的死亡,而不影响移植物抗肿瘤反应。
IF 5 3区 医学
Immunology Pub Date : 2025-06-25 DOI: 10.1111/imm.70010
Bárbara Betônico Berg, Zara Desiree Tonidandel Campos, Gioconda Muniz Fiorenza Ruggio, Ana Flávia Santos Linhares, Bárbara Maximino Rezende, Stêfany Bruno de Assis Cau, Thiago Roberto Lima Romero, Mauro Martins Teixeira, Vanessa Pinho, Marina Gomes Miranda Castor
{"title":"Palmitoylethanolamide (PEA) Induces an Increase in Spleen Regulatory T Cells, Reduces CD8\u0000 + Cells and TNF-α Levels in Target Organs, and Protects Mice From Graft-Versus-Host Disease-Related Mortality Through PPAR Activation Without Compromising the Graft-Versus-Tumour Response","authors":"Bárbara Betônico Berg,&nbsp;Zara Desiree Tonidandel Campos,&nbsp;Gioconda Muniz Fiorenza Ruggio,&nbsp;Ana Flávia Santos Linhares,&nbsp;Bárbara Maximino Rezende,&nbsp;Stêfany Bruno de Assis Cau,&nbsp;Thiago Roberto Lima Romero,&nbsp;Mauro Martins Teixeira,&nbsp;Vanessa Pinho,&nbsp;Marina Gomes Miranda Castor","doi":"10.1111/imm.70010","DOIUrl":"10.1111/imm.70010","url":null,"abstract":"<p>Graft-versus-host disease (GVHD), a secondary complication of bone marrow transplantation, leads to the development of a systemic inflammatory illness in the host, resulting in high mortality and morbidity. Current therapies lack prophylactic effectiveness and often fail to achieve an optimal immunological balance between inflammation and immunosuppression. In this study, we investigated the effects of palmitoylethanolamide (PEA), an endocannabinoid-like lipid mediator with extensively documented anti-inflammatory, analgesic, antimicrobial, immunomodulatory, and neuroprotective effects, on the complex pathology of GVHD. Treatment with PEA reduced clinical disease severity in GVHD mice, leading to an 80% increase in survival rates. Additionally, PEA created an immunoregulatory environment in the spleen by reducing the activation of CD3<sup>+</sup>CD4<sup>+</sup> cells. In the intestine, PEA protected against damage, reduced the number of CD3<sup>+</sup>CD4<sup>+</sup> and CD3<sup>+</sup>CD8<sup>+</sup> cells, and suppressed the activation of CD3<sup>+</sup>CD8<sup>+</sup> cells. PEA also decreased the levels of TNF-α in the intestine and increased IL-10 production. Furthermore, in the liver, PEA treatment reduced the number of CD8<sup>+</sup> cells, the activation of CD3<sup>+</sup>CD4<sup>+</sup> and CD3<sup>+</sup>CD8<sup>+</sup> cells, and TNF-α levels. The effect of PEA on survival was dependent on Peroxisome Proliferator-activated receptor gamma (PPAR-γ) activation but did not rely on cannabinoid (CB) receptors activation. In addition to GVHD protection, PEA treatment did not interfere in the graft-versus-tumour response. These results demonstrate the therapeutic potential of PEA as a promising option for the treatment of GVHD, balancing inflammation and immunosuppression, and improving both survival and clinical outcomes.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 3","pages":"385-402"},"PeriodicalIF":5.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Acute Plasmodium yoelii 17XNL Infection During BCG Vaccination Limits T Cell Responses and Mycobacterial Growth Inhibition 卡介苗接种期间急性约氏疟原虫17XNL感染限制T细胞反应和分枝杆菌生长抑制。
IF 5 3区 医学
Immunology Pub Date : 2025-06-19 DOI: 10.1111/imm.70006
Emily Tangie, Nawamin Pinpathomrat, Rachel Tanner, Nai-Jen Hsu, Alexandra J. Spencer, Muazzam Jacobs, Helen Mcshane, Roanne Keeton
{"title":"Acute Plasmodium yoelii 17XNL Infection During BCG Vaccination Limits T Cell Responses and Mycobacterial Growth Inhibition","authors":"Emily Tangie,&nbsp;Nawamin Pinpathomrat,&nbsp;Rachel Tanner,&nbsp;Nai-Jen Hsu,&nbsp;Alexandra J. Spencer,&nbsp;Muazzam Jacobs,&nbsp;Helen Mcshane,&nbsp;Roanne Keeton","doi":"10.1111/imm.70006","DOIUrl":"10.1111/imm.70006","url":null,"abstract":"<p>Tuberculosis and malaria overlap in many sub-Saharan African countries where Bacillus Calmette Guérin (BCG) vaccination is routinely administered. The aim of this study was to determine whether the timing of BCG vaccination in relation to a malaria infection has implications for BCG vaccine efficacy. Mice were intradermally vaccinated with BCG either 4 weeks before infection with blood-stage <i>Plasmodium yoelii 17XNL</i>, at 13 days post-infection (during an acute blood-stage malaria infection) or 21 days post-infection (after clearance of <i>P. yoelii 17XNL</i> infection). Ex vivo control of mycobacterial growth by splenocytes was used as a surrogate of protective efficacy, and PPD-specific T-cell responses were quantified by flow cytometry. No differences in mycobacterial growth control were detected between BCG vaccinated mice and groups receiving vaccination prior to or after clearance of <i>P. yoelii 17XNL</i> infection. Poorer control of mycobacterial growth was observed following BCG vaccination administered during an acute malarial infection compared to BCG vaccination only or BCG vaccination after blood-stage malaria infection, and mycobacterial growth negatively correlated with the magnitude of total cytokine production from PPD-specific CD4<sup>+</sup> T cells (<i>p</i> &lt; 0.0001). Delayed BCG vaccination beyond the neonatal period may increase the risk of concurrent malarial infections with the potential to reduce BCG efficacy in children in malaria-endemic areas.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 3","pages":"373-384"},"PeriodicalIF":5.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
CD59, Disulphide-Locked Human C9 and Horse C9 Inhibit Human Membrane Attack Complex Assembly by Similar Mechanisms CD59,二硫化物锁定的人C9和马C9通过相似的机制抑制人膜攻击复合物组装。
IF 5 3区 医学
Immunology Pub Date : 2025-06-16 DOI: 10.1111/imm.70008
Rebekah S. Cooke, Bradley A. Spicer, Richard A. Harrison, Michelle A. Dunstone, B. Paul Morgan, Wioleta M. Zelek
{"title":"CD59, Disulphide-Locked Human C9 and Horse C9 Inhibit Human Membrane Attack Complex Assembly by Similar Mechanisms","authors":"Rebekah S. Cooke,&nbsp;Bradley A. Spicer,&nbsp;Richard A. Harrison,&nbsp;Michelle A. Dunstone,&nbsp;B. Paul Morgan,&nbsp;Wioleta M. Zelek","doi":"10.1111/imm.70008","DOIUrl":"10.1111/imm.70008","url":null,"abstract":"<p>Five plasma proteins, C5b, C6, C7, C8 and C9, assemble in a step-wise manner to form the membrane attack complex (MAC) which inserts into target cell membranes to cause lysis. The membrane regulator CD59 binds nascent C5b-8, preventing C9 recruitment and polymerisation into the lytic pore. A disulphide-locked C9 (‘C9lock’; C9<sub>F262C/V405C</sub>) lacked haemolytic activity in standard assays because the unfolding required for pore formation was prevented, while horse C9 (HoC9) lacked haemolytic activity suggested to be a consequence of species incompatibility in MAC assembly. In this study, we compared the impact of soluble CD59 (sCD59), C9lock and HoC9 on MAC assembly. C9lock and sCD59 were generated recombinantly, while HoC9 and human C9 (HuC9) were affinity-purified from serum. Binding and haemolytic assays were used to identify and compare the modes of action of MAC binding and inhibition by sCD59, C9lock and HoC9. We show that sCD59, C9lock and HoC9 all inhibited human serum mediated haemolysis in both classical and alternative pathways. In reactive lysis assays, all three inhibitors bound immobilised C5b-8 but not C5b-7 intermediates on ELISA wells and gpE, and competitively blocked C9-mediated lysis of gpE. Each of the inhibitors also bound mouse and rat C5b-8 sites on gpE and blocked human C9-mediated lysis. This work clarifies the functional differences between HoC9 and human C9 and highlights the mechanistic similarities of the diverse MAC inhibitors (C9lock, sCD59 and HoC9). These agents not only provide useful tools for analysis of MAC assembly but also signpost novel strategies for specific MAC inhibition in conditions where MAC formation contributes to pathology.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"176 3","pages":"363-372"},"PeriodicalIF":5.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Should We Advance Our Understanding of Immunoglobulin E in Viral Immunity? 免疫球蛋白E在病毒免疫中的作用?
IF 5 3区 医学
Immunology Pub Date : 2025-06-13 DOI: 10.1111/imm.70007
Amanda Izeli Portilho, Valéria Oliveira Silva, Luis Fernando de Macedo Brigido, Elizabeth De Gaspari
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