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Microglial Response to Aspergillus flavus and Candida albicans: Implications in Endophthalmitis
Jaishree Gandhi1,2, Poonam Naik1,2, Inderjeet Kaur3
1Jhaveri Microbiology Centre, Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Hyderabad, Telangana 500034, India.
Abstract:
Aspergillus flavus is the most common etiology of fungal endophthalmitis in India, while Candida albicans is the causative agent in the West. In this study, we determined the role of microglial cells in evoking an inflammatory response following an infection with A. flavus and C. albicans strains isolated from patients with endophthalmitis. Microglia (CHME-3) cells were infected with A. flavus and C. albicans and the expression of Toll-Like Receptors (TLRs), cytokines and Matrix metalloproteinases (MMPs) were assessed at various time intervals. A. flavus infected cells induced higher expressions of TLR-1, -2, -5, -6, -7 and -9 and cytokines such as IL-1α, IL-6, IL-8, IL-10 and IL-17. In contrast, C. albicans infected microglia induced only TLR-2 along with the downregulation of IL-10 and IL-17. The expression of MMP-9 (Matrix metalloproteinase-9) was however upregulated in both A. flavus and C. albicans infected microglia. These results indicate that microglial cells have the ability to incite an innate response towards endophthalmitis causing fungal pathogens via TLRs and inflammatory mediators. Moreover, our study highlights the differential responses of microglia towards yeast vs. filamentous fungi.
Insights
Microglial cells mount an inflammatory response to fungal endophthalmitis pathogens. Aspergillus flavus triggers a stronger response via Toll-Like Receptors (TLRs) and cytokines than Candida albicans.
Area of Science:
- Ophthalmology
- Immunology
- Microbiology
Background:
- Fungal endophthalmitis is a severe intraocular infection.
- Aspergillus flavus and Candida albicans are common causes of endophthalmitis globally.
- Microglia are key immune cells in the central nervous system.
Purpose of the Study:
- To investigate the role of microglial cells in the inflammatory response to Aspergillus flavus and Candida albicans.
- To compare the differential immune responses of microglia to these two fungal pathogens.
Main Methods:
- Human microglia (CHME-3) cells were infected with Aspergillus flavus and Candida albicans.
- The expression of Toll-Like Receptors (TLRs), cytokines, and Matrix metalloproteinases (MMPs) was measured.
- Quantitative analysis of gene and protein expression was performed at various time points.
Main Results:
- Aspergillus flavus infection significantly upregulated TLR-1, -2, -5, -6, -7, -9, and multiple cytokines (IL-1α, IL-6, IL-8, IL-10, IL-17).
- Candida albicans infection primarily upregulated TLR-2, with downregulation of IL-10 and IL-17.
- Matrix metalloproteinase-9 (MMP-9) was upregulated by both fungal species.
Conclusions:
- Microglial cells initiate an innate immune response to fungal endophthalmitis pathogens through TLRs and inflammatory mediators.
- Microglia exhibit distinct responses to yeast (Candida albicans) versus filamentous fungi (Aspergillus flavus).
- Understanding these differential responses is crucial for developing targeted therapies for fungal endophthalmitis.
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