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
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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.

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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。
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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.
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