Publication Date:
2013-07-11
Description:
The pathogenesis of fungal infection in the cornea remains largely unclear. To understand how the immune system influences the progression of fungal infection in corneas, we inoculated immunocompetent Balb/c mice, neutrophil- or CD4 + T-cell-depleted Balb/c mice and nude mice with Candida albicans . We found that only immunocompetent Balb/c mice developed typical Candida keratitis (CaK), while the other mouse strains lacked obvious clinical manifestations. Furthermore, CaK development was blocked in immunocompetent mice treated with anti-IL-17A or anti-IL-23p19 to neutralize IL-17 activity. However, no significant effects were observed when Treg cells, γδ T cells or IFN-γ were immunodepleted. Upon infection, the corneas of Balb/c mice were infiltrated with IL-17-producing leukocytes, including neutrophils and, to a lesser degree, CD4 + T cells. In contrast, leukocyte recruitment to corneas was significantly diminished in nude mice. Indeed, nude mice produced much less chemokines (e.g. CXCL1, CXCL2, CLCL10, CLCL12, CCL2 and IL-6) in response to inoculation. Remarkably, addition of CXCL2 during inoculation restored CaK induction in nude mice. In contrast to its therapeutic effect on CaK, neutralization of IL-17 exacerbated Candida -induced dermatitis in skin. We conclude that IL-17, mainly produced by neutrophils and CD4 + T cells in the corneas, is essential in the pathogenesis of CaK. This article is protected by copyright. All rights reserved
Print ISSN:
0014-2980
Electronic ISSN:
1521-4141
Topics:
Medicine
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