Open Access

ARTICLE

Single-cell transcriptomics reveals T-cell heterogeneity and immunomodulatory role of CD4⁺ T native cells in Candida albicans infection

KERAN JIA¹, YANHAO ZHANG¹, MENGYU JIANG², MENGGE CUI², JIA WANG², JIAJIA ZHANG², HUIHAI ZHAO², MENGYAN LI², HUA WANG², QUANMING ZOU^1,#,*, HAO ZENG^1,#,*

1 National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, 400038, China
2 Department of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital), Shijiazhuang, 050082, China

* Corresponding Authors: QUANMING ZOU. Email: ; HAO ZENG. Email:
# These authors have contributed equally to this work

(This article belongs to the Special Issue: Cell Death and Inflammation in Signaling and Diseases)

BIOCELL 2024, 48(9), 1355-1368. https://doi.org/10.32604/biocell.2024.051383

Received 04 March 2024; Accepted 12 June 2024; Issue published 04 September 2024

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 (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.

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