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      IL-17 Promotes Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas

      , , ,
      The Journal of Immunology
      The American Association of Immunologists

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          Abstract

          The aim of this study was to elucidate the expression and functions of Interleukin (IL)-17 in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa (PA) infection. We found that PA -infection induced an increased signaling of IL-23/23R/17/17R in mouse corneas Targeting IL-17A or the IL-17A-specific receptor IL-17RA/IL-17RC with neutralizing antibodies resulted in a significant decrease in the severity of PA keratitis, including a decrease in bacterial burden and PMN infiltration. IL-17A signaling blockade also significantly reduced the expression of the pro-inflammatory cytokines L-1β, IL-24, and MMP-13 and increased the expression of the anti-inflammatory cytokine IL-1RA in mouse corneal epithelium. The presence of mouse IL-17A exacerbated PA -mediated tissue destruction. A cytokine protein array revealed that the expression of Osteoprotegerin (OPG) was regulated by IL-17A, and OPG neutralization also resulted in a decrease in the severity of PA keratitis. While both IL-17 and OPG affected the balanced expression of IL-1β and IL-1RA, only IL-17 inhibited the expression of TH2 cytokines. Taken together, our results revealed that IL-17A, along with its downstream factor OPG, plays a detrimental role in the pathogenesis of PA keratitis. Targeting IL-17A and/or the OPG/RANKL/RANK/TRAIL system is a potential therapeutic strategy in controlling the outcome of PA keratitis which was demonstrated by concurrent topical application of IL-17A neutralizing antibody and ciprofloxacin in B6 mice.

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          Author and article information

          Contributors
          (View ORCID Profile)
          Journal
          The Journal of Immunology
          J.I.
          The American Association of Immunologists
          0022-1767
          1550-6606
          December 17 2019
          January 01 2020
          January 01 2020
          November 25 2019
          : 204
          : 1
          : 169-179
          Article
          10.4049/jimmunol.1900736
          6920547
          31767781
          4863e238-5884-4324-9843-10ef00aa461c
          © 2019
          History

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