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.
Highlights
Fungal endophthalmitis is a rare clinical entity globally, in tropical countries such as India and China, this incidence varies from 17–30% of the total cases seen and represents a significant problem, associated with a delayed diagnosis and poor prognosis [1]
Toll-Like Receptors’ (TLRs) Expression Profile in Response to Aspergillus flavus and Candida albicans in Microglia
Comparing the expression between the two fungal pathogens, we found that microglial cells infected with A. flavus were significantly upregulated in IL-8 (p < 0.05), IL-10 (p < 0.005) and IL-17 (p < 0.005) at 12 h p.i. whereas in C. albicans infected cells these mediators were upregulated in IL-8 (p < 0.05), IL-10 (p < 0.005) and IL-17 (p < 0.005) at 12 h p.i. whereas in C. albicans downregulated the indicated
Summary
Fungal endophthalmitis is a rare clinical entity globally, in tropical countries such as India and China, this incidence varies from 17–30% of the total cases seen and represents a significant problem, associated with a delayed diagnosis and poor prognosis [1]. (yeast) is the most frequent pathogen reported from the Western countries such as the USA and Europe, in tropical countries such as India, the etiology of fungal pathogens includes Aspergillus sp. Fungal endophthalmitis due to yeast (Candida albicans) are usually endogenous and differ from filamentous fungi (Aspergillus or Fusarium sp.). The major mechanism responsible for increased virulence in clinical Candida isolates in addition to viral coinfections is the overexpression of plasma membrane efflux pumps and the use of P-glycoprotein pump inhibitor associated drugs for the enhancement of antifungal activity is being proposed [5]. A previous study in our laboratory showed a high rate of detection
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