Pathogenic Aspergillus and Fusarium as important causes of blinding corneal infections - the role of neutrophils in fungal killing, tissue damage and cytokine production

Abstract

Filamentous fungi Aspergillus and Fusarium species are major causes of visual impairment and blindness in immune competent individuals. Once conidia penetrate the corneal epithelium and enter the stroma, they undergo germination, and exposure of cell wall components induces a pronounced neutrophil-rich cellular infiltrate. In this review, we discuss Aspergillus and novel Fusarium virulence factors that are required for corneal infection, and describe the multiple functions of neutrophils in limiting hyphal growth in the cornea. This review will also discuss the role of neutrophils as an important source of cytokines in fungal keratitis, and highlight recent studies identifying unique characteristics of neutrophil secretion of IL-1α and IL-1β.

Figure 1. Neutrophils are the predominant cells in corneal ulcers caused by Aspergillus.

(a) The human eye. (b) Hematoxylin & eosin (H&E)-stained section of a normal, healthy human cornea showing the epithelial, stromal, and endothelial layers that work together to maintain corneal transparency and clear vision. (c) Gomori methenamine silver (GMS)-stained cornea from a patient infected with A. flavus keratitis following corneal transplantation. (d) Fusarium keratitis patient showing central corneal opacification and a hypopyon in the anterior chamber, which is comprised primarily of neutrophils. (e) Scraping from a corneal ulcer showing A. flavus hyphae (left panel) and Wrights-Giemsa stained cells (right panel). Highlighted areas show neutrophils. (f) Percentage of neutrophils and mononuclear cells in corneal ulcers caused by Fusarium and Aspergillus (data points represent individual patients). (a–c) reprinted from Leal and Pearlman [65], Copyright © 2012 Elsevier Inc. with permission from Elsevier. (d) Stock photo from Google Images. (e) and (f) reproduced with permission from Karthikeyan et al. [13].

Figure 2

IL-1α and IL-1β secretion by neutrophils compared with macrophages. See text for details.