title: IL-17A-mediated protection against Acanthamoeba keratitis.
abstract: Acanthamoeba keratitis (AK) is a very painful and vision-impairing infection of the cornea that is difficult to treat. Although past studies have indicated a critical role of neutrophils and macrophages in AK, the relative contribution of the proinflammatory cytokine, IL-17A, that is essential for migration, activation, and function of these cells into the cornea is poorly defined. Moreover, the role of the adaptive immune response, particularly the contribution of CD4(+) T cell subsets, Th17 and regulatory T cells , in AK is yet to be understood. In this report, using a mouse corneal intrastromal injection-induced AK model, we show that Acanthamoeba infection induces a strong CD4(+) T effector and regulatory T cell response in the cornea and local draining lymph nodes. We also demonstrate that corneal Acanthamoeba infection induces IL-17A expression and that IL-17A is critical for host protection against severe AK pathology. Accordingly, IL-17A neutralization in Acanthamoeba-infected wild-type mice or Acanthamoeba infection of mice lacking IL-17A resulted in a significantly increased corneal AK pathology, increased migration of inflammatory cells at the site of inflammation, and a significant increase in the effector CD4(+) T cell response in draining lymph nodes. Thus, in sharp contrast with other corneal infections such as herpes and Pseudomonas aeruginosa keratitis where IL-17A exacerbates corneal pathology and inflammation, the findings presented in this article suggest that IL-17A production after Acanthamoeba infection plays an important role in host protection against invading parasites.
authors.affiliation: New England Eye Center, Boston, MA 02111; Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02111; and.
authors.forename: Amol
authors.initials: A
authors.lastname: Suryawanshi
authors.affiliation: New England Eye Center, Boston, MA 02111; Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02111; and.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Cao
authors.affiliation: New England Eye Center, Boston, MA 02111; Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02111; and.
authors.forename: James F
authors.initials: JF
authors.lastname: Sampson
authors.affiliation: New England Eye Center, Boston, MA 02111; Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02111; and Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111 Noorjahan.Panjwani@tufts.edu.
authors.forename: Noorjahan
authors.initials: N
authors.lastname: Panjwani
mesh_terms: D000048:Acanthamoeba / Q000276:immunology*; D015823:Acanthamoeba Keratitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D003315:Cornea / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007111:Immunity, Cellular; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17