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 ZOU1,#,*, HAO ZENG1,#,*
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 Author: QUANMING ZOU. Email: 
; HAO ZENG. Email: 
(This article belongs to the Special Issue: Cell Death and Inflammation in Signaling and Diseases)
BIOCELL https://doi.org/10.32604/biocell.2024.051383
Received 04 March 2024; Accepted 12 June 2024; Published online 26 July 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-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.
Keywords
Candida albicans; Single-cell transcriptomics; Immune microenvironment; Fungal infections; Hub gene
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