ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Fungal Pathogenesis
This article is part of the Research TopicMechanisms of Immune Response and Evasion in Fungal PathogenesisView all articles
PFKFB3 Alleviates the Advancement of Fusarium Solani Keratitis by Attenuating Macrophage Inflammation
Provisionally accepted
- Fujian Medical University Union Hospital, Fu Zhou, China
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Objective: To investigate the anti-inflammatory effect of glycolysis rate-limiting enzyme 6-phosphofructose-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) in fungal keratitis (FK) infected by Fusarium solani (F. solani). Methods: We identified the up-regulation of PFKFB3 in fungal keratitis via western blot, quantitative real-time polymerase chain reaction (RT-PCR), and immunofluorescence staining. Subsequently, elucidated the augmentation of glycolytic flux in cornea and bone marrow-derived macrophages (BMDM) following F. solani invasion by RT-PCR, cellular energy metabolism analyzer, and lactate content assay. After that, we reduced PFKFB3 expression utilizing small interfering RNA (siRNA) in vitro and adeno-associated virus (AAV) in vivo and also assessed the expression levels of inflammatory factors. The severity of corneal infection following PFKFB3 depletion was checked by slit-lamp microscopy, corneal OCT, and H&E staining. Ultimately, we assessed the phosphorylation status of the PI3K/AKT/NF-κB p65 signaling pathway following PFKFB3 suppression via western blot and immunofluorescence staining. Results: PFKFB3 was highly triggered in F. solani-infected corneas and BMDM compared to normal tissue. Besides, infection with F. solani promotes the increase of inflammatory mediators and glycolytic flux in the cornea and BMDM. Whereas inflammation in BMDM and the degree of fungal keratitis lesions worsen by suppressing PFKFB3 expression, which increased corneal ulcer infiltration, elevated clinical scores, enhanced corneal thickness, and upregulation of inflammatory signals could be demonstrated. Furthermore, we found that F. solani infection can activate the phosphorylation of PI3K/AKT/NF-κB p65 at low PFKFB3 expression levels. Conclusions: In F. solani-infected corneas and BMDM, the glycolysis rate-limiting enzyme PFKFB3 was markedly upregulated. After infection, moderate PFKFB3 activation effectively mitigates inflammation and the progression of fungal keratitis. Moreover, activated PFKFB3 may rely on the PI3K/AKT/NF-κB p65 signaling pathway to safeguard the cornea from further damage due to inflammation.
Keywords: Fungal keratitis, Inflammation, PFKFB3, BMDM, Glycolysis
Received: 05 May 2025; Accepted: 19 Nov 2025.
Copyright: © 2025 Zhang, Zhang, Tang and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jianzhang Hu, ophhjz@163.com
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