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Temporal Transcriptomic Profiling Reveals DECTIN-1-Mediated Immune Responses in Acanthamoeba Keratitis
Jinding Pang1, Zhenyu Wei1, Yuheng Zhang1
1Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China.
Purpose:
The purpose of this study was to investigate the dynamic immune response and the role of DECTIN-1 in Acanthamoeba keratitis (AK).
Methods:
The AK mouse model was established, and corneal tissue samples were collected at 1, 3, and 7 days post-infection (dpi). Transcriptomic profiling was performed to analyze differentially expressed genes and enriched Gene Ontology terms. Immune cell infiltration was estimated using ImmuCellAI-mouse. The expression of DECTIN-1 and associated signaling molecules was validated using quantitative PCR, immunostaining, and Western blotting. In vitro experiments were conducted to assess DECTIN-1 expression in human corneal epithelial cells (HCECs).
Results:
AK progression was characterized by dynamic changes, with peak inflammatory responses at 3 dpi. Immune infiltration analysis revealed early innate immune activation followed by adaptive immune involvement at later stages. Temporal transcriptome analysis identified DECTIN-1 as a significantly upregulated gene throughout disease progression. Activation of the DECTIN-1/SYK/NF-κB signaling pathway was associated with increased expression of pro-inflammatory cytokines. In vitro experiments confirmed that Acanthamoeba directly induced DECTIN-1 expression in HCECs.
Conclusions:
DECTIN-1 was dynamically upregulated during AK and may play a potential role in mediating innate immune responses and shaping immune cell dynamics. These findings provided new insights into AK pathogenesis and indicated DECTIN-1 as a potential therapeutic target.