Single-cell transcriptomics reveals T-cell heterogeneity and immunomodulatory role of CD4<sup>+</sup> T native cells in <i>Candida albicans</i> infection

Abstract

Objective: Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms, including coordinated innate and adaptive immune responses, to neutralize invading fungi effectively. Exploring the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal infections. Methods: The study analyzed individual immune cell profiles in peripheral blood mononuclear cells from Candida albicans-infected mice and healthy control mice using single-cell transcriptomics, fluorescence quantitative PCR, and Western blotting. We investigated intergroup differences in the dynamics of immune cell subpopulation infiltration, pathway enrichment, and differentiation during Candida albicans infection. Results: Our findings indicate that infiltration of CD4 naive cells, regulatory T (Treg) cells, and Microtubules-associated (MT)-associated cells increased after infection, along with impaired T cell activity. Notably, CD4 T cells and plasma cells were enhanced after infection, suggesting that antibody production is dependent on T cells. In addition, we screened 6 hub genes, transcription factor forkhead box protein 3(Foxp3), cytotoxic T-lymphocyte associated protein 4 (CTLA4), Interleukin 2 Receptor Subunit Beta (Il2rb), Cd28, C-C Motif Chemokine Ligand 5 (Ccl5), and Cd27 for alterations associated with CD4 T cell differentiation. Conclusions: These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections.