McCulloch, Timothy R., Rossi, Gustavo R., Miranda-Hernandez, Socorro, Valencia-Hernandez, Ana Maria, Alim, Louisa, Belle, Clemence J., Krause, Andrew, Zacchi, Lucia F., Lam, Pui Yeng, Nakamura, Kyohei, Kupz, Andreas, Wells, Timothy J., and Souza-Fonseca-Guimaraes, Fernando (2024) The immune checkpoint TIGIT is upregulated on T cells during bacterial infection and is a potential target for immunotherapy. Immunology and Cell Biology, 102 (8). pp. 721-733.

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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.

Item ID:	83716
Item Type:	Article (Research - C1)
ISSN:	1440-1711
Keywords:	CD4 T cells +,immunotherapy,Salmonella Typhimurium,TIGIT
Related URLs:	https://www.scopus.com/inward/record.uri...
Copyright Information:	© 2024 The Author(s). Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Funders:	National Health and Medical Research Council (NHMRC)
Projects and Grants:	NHMRC Investigator Grant Number: APP2008715
Date Deposited:	23 Sep 2024 23:37
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