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Updated: Jun 27, 2025
Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Global Transcriptomic Profiling of Innate and Adaptive Immunity During Aspergillus flavus Endophthalmitis in a Murine
Agimanailiu Khapuinamai1,2, Dhanwini Rudraprasad1,2, Suchita Pandey1
1Jhaveri Microbiology Centre, Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad, Telangana, India.
Purpose:
Fungal endophthalmitis is characterized by chronic inflammation leading to the partial or complete vision loss. Herein, we analyzed the transcriptomic landscape of Aspergillus flavus (A. flavus) endophthalmitis in C57BL/6 mice to understand the host-pathogen interactions.
Methods:
Endophthalmitis was induced by intravitreal injection of A. flavus spores in C57BL/6 mice and monitored for disease progression up to 72 hours. The enucleated eyeballs were subjected to histopathological analysis and mRNA sequencing using the Illumina Nextseq 2000. Pathway enrichment analysis was performed to further annotate the functions of differentially expressed genes (DEGs) and validation of cytokines was performed in vitreous of patients with fungal endophthalmitis using multiplex ELISA.
Results:
Transcriptomic landscape of A. flavus endophthalmitis revealed upregulated T-cell receptor signaling, PI3K-AKT, MAPK, NF-κB, JAK-STAT, and NOD like receptor signaling pathways. We observed significant increase in the T-cells during infection especially at 72 hours infection along with elevated expression levels of IL-6, IL-10, IL-12, IL-18, IL-19, IL-23, CCR3, and CCR7. Furthermore, host-immune response associated genes, such as T-cell interacting activating receptor, TNF receptor-associated factor 1, TLR1, TLR9, and bradykinin receptor beta 1, were enriched. Histopathological assessment validated the significant increase in inflammatory cells, especially T-cells at 72 hours post-infection along with increased disruption in the retinal architecture. Additionally, IL-6, IL-8, IL-17, TNF-α, and IL-1β were also significantly elevated, whereas IL-10 was downregulated in vitreous of patients with Aspergillus endophthalmitis.
Conclusions:
Regulating T-cell influx could be a potential strategy to modulate the excessive inflammation in the retina and potentially aid in better vision recovery in fungal endophthalmitis.
Insights
This study reveals key immune pathways activated during Aspergillus flavus fungal endophthalmitis in mice. Modulating T-cell responses may improve vision recovery in fungal eye infections.
Area of Science:
- Ophthalmology
- Mycology
- Immunology
Background:
- Fungal endophthalmitis causes chronic inflammation and vision loss.
- Understanding host-pathogen interactions is crucial for effective treatment.
Purpose of the Study:
- To analyze the transcriptomic landscape of Aspergillus flavus (A. flavus) endophthalmitis.
- To elucidate host-pathogen interactions in a murine model.
Main Methods:
- Intravitreal injection of A. flavus spores in C57BL/6 mice.
- Transcriptomic analysis (mRNA sequencing) and histopathology.
- Validation of cytokine levels in human vitreous samples.
Main Results:
- Upregulation of T-cell receptor, PI3K-AKT, MAPK, NF-κB, JAK-STAT, and NOD-like receptor signaling pathways.
- Increased T-cells and elevated inflammatory cytokines (IL-6, IL-12, IL-18, etc.) observed.
- Histopathology confirmed increased inflammatory cells and retinal damage; human samples showed elevated IL-6, IL-8, IL-17, TNF-α, and decreased IL-10.
Conclusions:
- T-cell influx plays a significant role in the inflammatory response.
- Regulating T-cell responses could be a therapeutic strategy for fungal endophthalmitis.
- Potential for improved vision recovery through targeted immunomodulation.
