title: IL-17 plays a central role in initiating experimental Candida albicans infection in mouse corneas.
abstract: 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, CXCL10, CXCL12, 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.
authors.affiliation: Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, P. R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zou
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Dong
authors.forename: Wengang
authors.initials: W
authors.lastname: Song
authors.forename: Changkai
authors.initials: C
authors.lastname: Jia
authors.forename: Siyuan
authors.initials: S
authors.lastname: Li
authors.forename: Haijie
authors.initials: H
authors.lastname: Xi
authors.forename: Dongmin
authors.initials: D
authors.lastname: Liu
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000150:complications / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D054426:Chemokine CXCL2 / Q000008:administration & dosage; D018925:Chemokines / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D007634:Keratitis / Q000276:immunology* / Q000382:microbiology*; D047589:Leukocyte Reduction Procedures; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D023421:Models, Animal; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D054426:Chemokine CXCL2; D018925:Chemokines; D020381:Interleukin-17
keywords: Candida albicans; Corneal infection; Fungal infection; IL-17; Neutrophil