Chemokine CXCL1/KC and its receptor CXCR2 are responsible for neutrophil chemotaxis in adenoviral keratitis

Epidemic keratoconjunctivitis (EKC), caused by human adenovirus (HAdV), is one of the most common ocular infections and results in corneal infl ammation and subepithelial infi ltrates. Adenoviral keratitis causes significant morbidity to the patients, and is characterized by infi ltration of leukocytes in the corneal stroma, and expression of chemokines. The exact role of these chemokines in adenoviral infection has not been studied due to lack of animal models. Here, we have characterized the role of chemokine CXCL1/KC and receptor CXCR2 in adenoviral keratitis using a novel mouse model. Analysis of chemokine expression, leukocyte infi ltration, and development of keratitis was performed by ELISA, fl ow cytometry, and histopathology, respectively. Defi ciency of CXCL1 and CXCR2 resulted in delayed infi ltration of neutrophils, but not infl ammatory monocytes in HAdV-37 corneal infection. CXCL1-/- mice showed decreased expression of CXCL2/MIP-2, but not CCL2/MCP-1. CXCR2-/- mice showed increased expression of CXCL1 and CXCL2, but not CCL2. Both CXCL1-/- and CXCR2-/- mice demonstrated keratitis similar to wild-type mice. In conclusion, both CXCL1 and CXCR2 play an important role in chemokine expression and neutrophil infi ltration following adenoviral corneal infection, but have a redundant role in the development of keratitis.