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Amol Suryawanshi, Zhiyi Cao, Tanveer Zaidi, Noorjahan Panjwani; Galectin-1-Mediated Suppression of Th17 Cell-Induced Corneal Immunopathology post Pseudomonas aeruginosa Infection. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5211.
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© ARVO (1962-2015); The Authors (2016-present)
Although, past studies have indicated the critical role of CD4+ T cells, particularly the Th1 cells, in P. aeruginosa keratitis, the relative contribution of recently discovered Th17 and Treg cells is unclear. The goal of this study was to define the role of different CD4+ T cells subsets in P. aeruginosa-induced corneal immunopathology, and to characterize the role of a carbohydrate-binding protein, galectin-1 (Gal-1), in modulating the balance of various CD4+ T cells subsets and the associated P. aeruginosa-induced corneal pathology.
Corneal P. aeruginosa infected B6 mice corneas and local draining lymph nodes (DLN) were analyzed on day 5 and day 8 post infection (pi) for CD4+ T cells, Th1, Th17 and Treg cell composition by flow cytometry. In another set of experiments, infected B6 mice were treated with recombinant galectin-1 (rGal-1) or control vehicle by sub-conjunctival injections every alternate day starting from day 1 until day 11 pi. On day 12 pi, corneas and DLN were collected to analyze the effect of rGal-1 treatment on various CD4+ T cell subsets by flow cytometry and cytokine levels for IL-17A, IL-10 and IL-4 in the cornea and DLN by ELISA.
Corneal P. aeruginosa infection induced a strong Th17 cell response as compared to Th1 response in the cornea and DLN at all tested days pi. Furthermore, there was induction of Treg response in the cornea and DLN, however, the relative proportion of Treg over Th17 diminished significantly as infection progressed to a more severe form. Administration of rGal-1 significantly diminished corneal pathology through multiple mechanisms. Accordingly, rGal-1 treated group showed significantly reduced infiltration of total leuckoctyes, neutrophils and CD4+ T cells in the cornea. Moreover, rGal-1 treatment significantly diminished proinflammatory Th17 response, whereas promoted antiinflammatory Treg and Th2 response in the cornea as well as DLN when compared to control vehicle treated mice.
Corneal P. aeruginosa infection induces both Teffector (Th17 dominant) and Treg response in the cornea. Moreover, increasing representation of antiinflammatory Treg and Th2 cells over Th17 cells using endogenously derived molecules such as Gal-1 diminishes corneal pathology and represents a novel therapeutic approach to control bacterial keratitis, a common cause of vision loss and blindness in humans worldwide.
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