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Amol Suryawanshi, Zhiyi Cao, James Sampson, Noorjahan A Panjwani; IL-17A-Mediated Protection against Acanthamoeba Keratitis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1689.
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Acanthamoeba Keratitis (AK) is a very painful and vision impairing condition 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 a proinflammatory cytokine, IL-17A that promotes migration, activation and function of neutrophils in the cornea is poorly defined. Moreover, the role of the adaptive immune response, particularly contribution of CD4+ T cell subsets such as Th17 and Tregs, in AK is yet to be understood.
C57BL/6 mice corneas were intrastromally injected with 2.5 × 104 Acanthamoebae for corneal infection. Acanthamoeba infected mice corneas and local draining lymph nodes (dLN) were analyzed on day 5 and day 8 post infection (pi) for neutrophils, CD4+ T cells, Th1, Th2, Th17 and Treg cell composition by flow cytometry. In another set of experiments, corneal IL-17A expression was analyzed on day 1, 3, 5 and 8 pi. Furthermore, infected mice were treated with anti-IL-17A or isotype monoclonal antibody every alternate day starting from day 1 until day 7 pi. The severity of AK was scored on day 1, 3, 5 and 7 pi. On day 8 pi, corneas and dLN were collected to analyze the effect of anti-IL-17A treatment on various CD4+ T cell subsets by flow cytometry.
Corneal Acanthamoeba infection induced both Teffector (Th1, Th2 and Th17) and regulatory T cell response in the cornea at all tested days pi. More importantly, our studies revealed that Acanthamoeba infection induces IL-17A expression and that IL-17A is essential for host protection against severe AK pathology. Accordingly, IL-17A neutralization in Acanthamoeba infected animals resulted in a significantly increased corneal AK pathology, increased migration of inflammatory cells at the site of inflammation and a significant increase in effector CD4+ T cell response in dLN. Further studies indicated that neutrophils and CD4+ T cells contribute to the source of IL-17A during early and late stages of AK respectively.
Corneal Acanthamoeba infection induces both Teffector and Treg response in the cornea. Moreover, in sharp contrast to other corneal infections such as Herpes and Pseudomonas aeruginosa keratitis where IL-17A exacerbates corneal pathology and inflammation, findings reported in this study indicate that IL-17A response after Acanthamoeba infection plays an important role in host protection against invading parasites.
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