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

Abstract

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.

Molecular cloning, expression, and purification, along with in silico epitope analysis of recombinant enolase proteins (a potential vaccine candidate) from Candida albicans and Candida auris

“…The study by Langenhorst et al highlighted the immunostimulatory and therapeutic potential of Enolase protein from C. albicans on human and mouse immune cells (Langenhorst et al, 2023). Another study demonstrated direct modulation of T cell responses against C. albicans infections (Daud et al, 2023). Our results suggest that Enolase epitopes augers well for designing an improved anti-Candida vaccine.…”

“…The crystal structure of Enolase protein from C. albicans is available and provides valuable insights into its pathogenesis, virulence, and potential as a therapeutic vaccine candidate (Li et al, 2022). The study by Langenhorst et al highlighted the immunostimulatory and therapeutic potential of Enolase protein from C. albicans on human and mouse immune cells (Langenhorst et al, 2023). Another study demonstrated direct modulation of T cell responses against C. albicans infections (Daud et al, 2023).…”