The immune checkpoint TIGIT is upregulated on T cells during bacterial infection and is a potential target for immunotherapy

IF 3.2 4区 医学 Q3 CELL BIOLOGY Immunology & Cell Biology Pub Date : 2024-06-14 DOI:10.1111/imcb.12794
Timothy R McCulloch, Gustavo R Rossi, Socorro Miranda-Hernandez, Ana Maria Valencia-Hernandez, Louisa Alim, Clemence J Belle, Andrew Krause, Lucia F Zacchi, Pui Yeng Lam, Kyohei Nakamura, Andreas Kupz, Timothy J Wells, Fernando Souza-Fonseca-Guimaraes
{"title":"The immune checkpoint TIGIT is upregulated on T cells during bacterial infection and is a potential target for immunotherapy","authors":"Timothy R McCulloch,&nbsp;Gustavo R Rossi,&nbsp;Socorro Miranda-Hernandez,&nbsp;Ana Maria Valencia-Hernandez,&nbsp;Louisa Alim,&nbsp;Clemence J Belle,&nbsp;Andrew Krause,&nbsp;Lucia F Zacchi,&nbsp;Pui Yeng Lam,&nbsp;Kyohei Nakamura,&nbsp;Andreas Kupz,&nbsp;Timothy J Wells,&nbsp;Fernando Souza-Fonseca-Guimaraes","doi":"10.1111/imcb.12794","DOIUrl":null,"url":null,"abstract":"<p>Antibiotic resistance is a major public health threat, and alternatives to antibiotic therapy are urgently needed. Immunotherapy, particularly the blockade of inhibitory immune checkpoints, is a leading treatment option in cancer and autoimmunity. In this study, we used a murine model of <i>Salmonella</i> Typhimurium infection to investigate whether immune checkpoint blockade could be applied to bacterial infection. We found that the immune checkpoint T-cell immunoglobulin and ITIM domain (TIGIT) was significantly upregulated on lymphocytes during infection, particularly on CD4<sup>+</sup> T cells, drastically limiting their proinflammatory function. Blockade of TIGIT <i>in vivo</i> using monoclonal antibodies was able to enhance immunity and improve bacterial clearance. The efficacy of anti-TIGIT was dependent on the capacity of the antibody to bind to Fc (fragment crystallizable) receptors, giving important insights into the mechanism of anti-TIGIT therapy. This research suggests that targeting immune checkpoints, such as TIGIT, has the potential to enhance immune responses toward bacteria and restore antibacterial treatment options in the face of antibiotic resistance.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12794","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunology & Cell Biology","FirstCategoryId":"2","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/imcb.12794","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Antibiotic resistance is a major public health threat, and alternatives to antibiotic therapy are urgently needed. Immunotherapy, particularly the blockade of inhibitory immune checkpoints, is a leading treatment option in cancer and autoimmunity. In this study, we used a murine model of Salmonella Typhimurium infection to investigate whether immune checkpoint blockade could be applied to bacterial infection. We found that the immune checkpoint T-cell immunoglobulin and ITIM domain (TIGIT) was significantly upregulated on lymphocytes during infection, particularly on CD4+ T cells, drastically limiting their proinflammatory function. Blockade of TIGIT in vivo using monoclonal antibodies was able to enhance immunity and improve bacterial clearance. The efficacy of anti-TIGIT was dependent on the capacity of the antibody to bind to Fc (fragment crystallizable) receptors, giving important insights into the mechanism of anti-TIGIT therapy. This research suggests that targeting immune checkpoints, such as TIGIT, has the potential to enhance immune responses toward bacteria and restore antibacterial treatment options in the face of antibiotic resistance.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
在细菌感染过程中,免疫检查点 TIGIT 在 T 细胞中上调,是免疫疗法的潜在靶点。
抗生素耐药性是一个重大的公共卫生威胁,因此迫切需要抗生素疗法的替代品。免疫疗法,尤其是阻断抑制性免疫检查点,是癌症和自身免疫的主要治疗选择。在这项研究中,我们使用鼠伤寒沙门氏菌感染模型来研究免疫检查点阻断是否可用于细菌感染。我们发现,在感染过程中,免疫检查点T细胞免疫球蛋白和ITIM结构域(TIGIT)在淋巴细胞上显著上调,尤其是在CD4+ T细胞上,极大地限制了它们的促炎功能。在体内使用单克隆抗体阻断 TIGIT 能够增强免疫力,提高细菌清除率。抗TIGIT的疗效取决于抗体与Fc(可结晶片段)受体结合的能力,这为了解抗TIGIT疗法的机制提供了重要依据。这项研究表明,靶向免疫检查点(如 TIGIT)有可能增强对细菌的免疫反应,并在抗生素耐药性面前恢复抗菌治疗选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Immunology & Cell Biology
Immunology & Cell Biology 医学-免疫学
CiteScore
7.50
自引率
2.50%
发文量
98
审稿时长
4-8 weeks
期刊介绍: The Australasian Society for Immunology Incorporated (ASI) was created by the amalgamation in 1991 of the Australian Society for Immunology, formed in 1970, and the New Zealand Society for Immunology, formed in 1975. The aim of the Society is to encourage and support the discipline of immunology in the Australasian region. It is a broadly based Society, embracing clinical and experimental, cellular and molecular immunology in humans and animals. The Society provides a network for the exchange of information and for collaboration within Australia, New Zealand and overseas. ASI members have been prominent in advancing biological and medical research worldwide. We seek to encourage the study of immunology in Australia and New Zealand and are active in introducing young scientists to the discipline.
期刊最新文献
Choose your own T-cell fate: creation of a narrative-based, decision-making activity to engage students in immunology. Identification of clonally expanded γδ T-cell populations during CAR-T cell therapy. Variations in the germinal center response revealed by genetically diverse mouse strains. The evolving role of mast cells in wound healing: insights from recent research and diverse models. ADAM10 modulates the efficacy of T-cell-mediated therapy in solid tumors.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1