Enolase 1 of Candida albicans binds human CD4 + T cells and modulates naïve and memory responses.

Autor: Daud M; Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany., Dasari P; Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany., Adelfinger M; Department of Internal Medicine II, Division of Hematology, University Hospital Würzburg, Würzburg, Germany., Langenhorst D; Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany., Lother J; Department of Internal Medicine II, Division of Hematology, University Hospital Würzburg, Würzburg, Germany., Slavkovic-Lukic D; Department of Internal Medicine II, Division of Hematology, University Hospital Würzburg, Würzburg, Germany., Berges C; Department of Internal Medicine II, Division of Hematology, University Hospital Würzburg, Würzburg, Germany., Kruhm M; Department of Internal Medicine II, Division of Hematology, University Hospital Würzburg, Würzburg, Germany., Galler A; T-Balance Therapeutics, Frankfurt, Germany., Schleussner C; T-Balance Therapeutics, Frankfurt, Germany., Luther CH; Chair of Bioinformatics, University of Würzburg, Würzburg, Germany., Alberter K; Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany., Althammer A; Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany., Shaikh H; Department of Internal Medicine II, Division of Hematology, University Hospital Würzburg, Würzburg, Germany., Pallmann N; Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany., Bodem J; Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany., El-Mowafy M; Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.; Faculty of Pharmacy, Department of Microbiology & Immunology, Mansoura University, Mansoura, Egypt., Beilhack A; Department of Internal Medicine II, Division of Hematology, University Hospital Würzburg, Würzburg, Germany., Dittrich M; Chair of Bioinformatics, University of Würzburg, Würzburg, Germany.; Institute of Human Genetics, University of Würzburg, Würzburg, Germany., Topp MS; Department of Internal Medicine II, Division of Hematology, University Hospital Würzburg, Würzburg, Germany., Zipfel PF; Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany.; Friedrich Schiller University, Jena, Germany., Beyersdorf N; Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2023 Nov; Vol. 53 (11), pp. e2250284. Date of Electronic Publication: 2023 Aug 10.
DOI: 10.1002/eji.202250284
Abstrakt: To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4 + T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4 + T-cell recall responses. Therapeutically, CD4 + T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4 + T cells with CaEno1 modulated host CD4 + T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4 + T-cell responses.
(© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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