Fungal keratitis (FK) is among the most dangerous ocular infections and can threaten eyesight if not properly controlled. The proportion of corneal infections caused by FK varies throughout the world. In New York in the 1980s, for example, approximately 1% of all observed infectious corneal diseases were designated FK,
1 whereas this number was 35% in Florida during that same period.
2 The best known predisposing factors include trauma in underdeveloped countries or contact lens wear in developed countries; hot and humid weather is a further risk factor in all countries.
3 Because of the specific structure of the cornea (thin and transparent) and the growth properties of fungi, FK manifests a fast and vicious progress and often leads to total sight loss in days. Better understanding of the pathogenesis of FK is necessary for the development of more effective therapeutics or intervening surgery. Unfortunately, progress in this field has been slow, and many issues remain unclear. For example, the molecular mechanisms underlying the interaction between pathogens and corneal components remain to be revealed, though it is agreed that filamentation of fungus mediated by molecules such as transcription factor or proteinase is critical for initiating the process.
4 5 The host reaction to corneal fungal invasion is also unclear. Large numbers of polymorphonuclear cells infiltrate the infected corneas, suggesting that innate immunity involving various Toll-like receptors (TLRs)
6 is the dominant host response to FK. We believe, however, that antigen-specific adaptive immunity is also involved in fighting the invading fungus. Our hypothesis is based mainly on existing data that abundant professional antigen-presenting cells, such as dendritic cells and macrophages, reside in the resting corneas and readily mature and migrate to draining lymph nodes on stimulation.
7 8 Adaptive immunity had been shown to be involved, as either a protective or a destructive factor, in the pathogenesis of keratitis caused by bacteria,
9 virus,
10 11 or acanthamoeba,
12 clearly demonstrating the capability of the cornea to start an adaptive immune response against pathogens. Wu et al.
13 observed that cyclophosphamide, a potent immunosuppressive drug that works primarily by inhibiting lymphocyte proliferation, increased the severity of FK, implying that lymphocytes might be involved in the pathogenesis of FK. In this study we confirm the hypothesis by showing that fungal infection of the cornea induces an adaptive immune response and an immunologic memory in host animals. Furthermore, we show for the first time that priming the murine immune systems by infecting other organs with live spores or by vaccination with inactivated spores helps to resist corneal infection by the same fungus.