ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Adaptive immunity in infection
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1560628
This article is part of the Research TopicEvolutionary adaptation in human-infecting fungi: Ecological traits and pathogenicityView all 3 articles
Fusarium spp. and Aspergillus flavus infection induce pathogen-specific and pathogenindependent host immune response in patients with fungal keratitis
Provisionally accepted
- Aravind Medical Research Foundation, Madurai, India
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Fungal keratitis, caused primarily by Fusarium spp. and Aspergillus flavus, is a significant cause of corneal blindness, particularly in tropical regions. Current antifungal agents like natamycin and voriconazole have limited efficacy, underscoring the need for a deeper understanding of host immune responses. This study employed high-throughput RNA sequencing to investigate differential gene expression in human corneal tissues from patients with Fusarium spp. and A.flavus keratitis and compared them to control cadaver corneal samples. RNA was extracted from infected and control samples, followed by sequencing and differential expression analysis. Data analysis identified common and Fusarium spp. and A. flavus-specific differentially expressed genes (DEGs). Pathway enrichment analysis using common genes identified pathways enriched in both infections, such as interleukin 17 (IL-17), tumor necrosis factor (TNF), and chemokine signalling. Expression of hub genes, including S100 calcium binding protein A7 (S100A7), S100 calcium binding protein A8 (S100A8), S100 calcium binding protein A9 (S100A9) and C-X-C motif chemokine ligand 8 (CXCL8), identified in interleukin 17 (IL-17) signalling, was confirmed by RT-qPCR analysis. Fusarium spp.-specific DEGs, including complement C3 (C3), interleukin 6 (IL-6), interleukin 19 (IL-19) and leucine rich alpha-2-glycoprotein 1 (LRG1), are enriched in pathways such as positive regulation of immune responses, acute inflammatory responses, leukocyte cell-cell adhesion, and the regulation of cell-cell adhesion. A. flavus-specific DEGs, such as triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E (APOE), are predominantly enriched in adaptive immune response, negative regulation of immune system process, negative regulation of immune response, cell migration and motility pathways. RT-qPCR confirmed the key pathogen-specific DEGs, highlighting their potential as biomarkers for pathogen-specific immune responses. These findings provide insights into the distinct immune pathways triggered by Fusarium spp. and A. flavus, offering new therapeutic targets for improving fungal keratitis treatment.
Keywords: Fungal keratitis (FK), Differential gene expression, pathogen specific host immune response, IL-17 signalling pathway, RT-qPCR analysis
Received: 14 Jan 2025; Accepted: 30 Apr 2025.
Copyright: © 2025 Dinesh, Prajna, Prajna, DHARMALINGAM and Devarajan. 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: Bharanidharan Devarajan, Aravind Medical Research Foundation, Madurai, India
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