Abstract
PURPOSE: To determine the role of the chemokine CXCL1 on leukocyte recruitment, cytokine production and host resistance during HSV-1 and Pseudomonas aeruginosa infection. METHODS: Viral titer and bacterial load were compared following infection of wild-type (WT) and CXCL1(-/-) mice. Corneal leukocyte recruitment was determined using flow cytometry. Cytokine levels were assessed by luminex-based suspension arrays. Hematoxylin and eosin (H&E) staining, confocal microscopy, and optical coherence tomography (OCT) were used to visualize leukocyte recruitment and corneal thickening. RESULTS: HSV-1-infected WT and CXCL1(-/-) mice possessed similar viral titers in the cornea during late acute infection. Flow cytometry analysis detected similar leukocyte levels in the cornea following infection as well. By comparison, there was a significant increase in P. aeruginosa recovered from CXCL1(-/-) corneas as compared with WT mice. Imaging analysis and histochemical staining revealed impaired leukocyte recruitment to the central cornea and earlier corneal thickening in CXCL1(-/-) mice. IFN-γ, CCL2, and CCL5 protein levels were similar between WT and CXCL1(-/-) corneas following HSV-1 or P. aeruginosa infection. However, CXCL2 levels were significantly reduced in the CXCL1(-/-) corneas following either infection. CONCLUSIONS: The absence of CXCL1 and CXCL2 expression significantly impairs the ability of the host to control P. aeruginosa replication through the recruitment of leukocytes to the central cornea. In contrast, CXCL1, CXCL2, and the cells they recruit, are not required for HSV-1 clearance during acute infection.