Role of contact lens wear, bacterial flora, and mannose-induced pathogenic protease in the pathogenesis of amoebic keratitis

Hassan Alizadeh, Sudha Neelam, Michael Hurt, Jerry Y. Niederkorn

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The ocular surface is continuously exposed to potential pathogens, including free-living amoebae. Acanthamoeba species are among the most ubiquitous amoebae, yet Acanthamoeba keratitis is remarkably rare. The pathogenesis of Acanthamoeba keratitis is a complex, sequential process. Here we show that Acanthamoeba keratitis is profoundly affected by mannosylated proteins on the ocular surface, which stimulate the amoebae to elaborate a 133-kDa pathogenic protease. The mannose-induced protease (MIP133) mediates apoptosis of the corneal epithelium, facilitates corneal invasion, and degrades the corneal stroma. We show that contact lens wear upregulates mannosylated proteins on the corneal epithelium, stimulates MIP133 secretion, and exacerbates corneal disease. Corynebacterium xerosis, a constituent of the ocular flora, contains large amounts of mannose and is associated with Acanthamoeba keratitis. The present results show that amoebae exposed to C. xerosis produce increased amounts of MIP133 and more severe corneal disease. Oral immunization with MIP133 mitigates Acanthamoeba keratitis and demonstrates the feasibility of antidisease vaccines for pathogens that resist immune elimination.

Original languageEnglish (US)
Pages (from-to)1061-1068
Number of pages8
JournalInfection and Immunity
Volume73
Issue number2
DOIs
StatePublished - Feb 2005

Fingerprint

Acanthamoeba Keratitis
Keratitis
Contact Lenses
Mannose
Amoeba
Peptide Hydrolases
Corneal Diseases
Corneal Epithelium
Acanthamoeba
Corneal Stroma
Corynebacterium
Immunization
Proteins
Up-Regulation
Vaccines
Apoptosis

ASJC Scopus subject areas

  • Immunology

Cite this

Role of contact lens wear, bacterial flora, and mannose-induced pathogenic protease in the pathogenesis of amoebic keratitis. / Alizadeh, Hassan; Neelam, Sudha; Hurt, Michael; Niederkorn, Jerry Y.

In: Infection and Immunity, Vol. 73, No. 2, 02.2005, p. 1061-1068.

Research output: Contribution to journalArticle

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