| Human adenovirus (HAdV) serotypes HAdV-8, 19 and 37 are major etiologic agents of epidemic keratoconjunctivitis (EKC). EKC results in formation of corneal subepithelial infiltrates and significant morbidity to the affected patient. We have developed a novel murine model to better understand the pathogenesis of adenovirus keratitis. Infection of stromal cells in the mouse cornea is achieved by intrastromal injection of HAdV-37. Utilizing this murine model we showed that chemokine CXCL1 and its receptor CXCR2 contribute to the infiltration of neutrophils in the cornea. We also determined the importance of various adenovirus-associated molecular patterns in the stimulation of in vivo innate immune responses. We demonstrate that empty viral capsid is sufficient to induce an innate immune response against adenoviral ocular infection resulting in corneal inflammation and expression of chemokines. In contrast, adenoviral gene expression, viral replication, viral DNA, and host TLR9 are not essential for the development of keratitis. This study represents a major advance in the understanding of pathogenesis of adenoviral ocular infection and adenoviral tissue infections in general. |
