Furthermore, IWR-1 clinical trial it was noteworthy that only a fraction of the Ly-6G+ cells were positive for IL-17 immunostaining (Fig. 4 and 5), and the remaining Ly-6G+ but IL-17− cells could be either neutrophils under heterogeneous status, or other Ly-6G+ resident myeloid cells such as monocytes in the cornea . Though IL-17 is generally involved in anti-infection responses , we show here that it can be detrimental to the clearance of pathogens in corneal tissue (Fig. 8). Considering that IL-17 expression is differentially regulated by different pathogens in the same cell , our conclusions concerning C. albicans may not be transferable to
infection of other pathogens. To address these concerns, we are currently undertaking comparative studies with other pathogens. In summary, we report that intrastromal inoculation Cabozantinib concentration of C. albicans blastospores does not cause keratitis in nude, IL-17A knockout, CD4+-depleted, neutrophil-depleted, and IL-23-/IL-17-neutralized mice. Our analysis of early events (<24 h) postinfection revealed that IL-17, mainly produced locally
by neutrophils and/or CD4+ T cells, played a central role in the initiation of CaK. Future studies will investigate the sequential or spatial regulation of IL-17 production, neutrophil activation, and immune compartments that interact with IL-17/Th17 in the context of FK. Taking into account the previous report that an adaptive immune response is required to protect the host from secondary CaK, we propose a biphasic mechanism of CaK pathogenesis: in early phase, CD4+ T cells act coordinately with neutrophils to initiate CaK in an IL-17-dependent manner, and later give way to adaptive immunity processes. All animal experiments were carried out in accordance with the Chinese Ministry of Science and Technology Guidelines on the Humane Treatment of Laboratory Animals (vGKFCZ-2006–398) and the Association for Research in Vision and Ophthalmology (ARVO) Statement for the Use of Animals in Ophthalmic
and Vision Research. This study and all protocols concerning animals were approved by the Shandong Eye Institute enough Review Board with permit number SEIRB-2009–2009CB526506. All animal experiments were carried out in accordance with the Guidelines on the Humane Treatment of Laboratory Animals (Chinese Ministry of Science and Technology, 2006) and the Statement for the Use of Animals in Ophthalmic and Vision Research. WT C57BL/6J mice, BALB/c mice, and nude mice with a BALB/c background (H-2d) were purchased from the Academy of Military Medical Sciences (Beijing, China). IL-17A-deficient (IL-17A−/−) mice that were backcrossed to C57BL/6J mice for over ten generations [45, 46] were provided by Dr. Chen Dong (M.D. Anderson Cancer Center, Houston, TX, USA). All animals were maintained in pathogen-free facility and were 6–10 weeks old when the experiments were performed.