Epithelial Heparan Sulfate Promotes

Cathelicidins are short cationic peptides with potent microbicidal activities and comprise an important arm of host innate immunity. Many cell types can produce cathelicidins, but they are mainly expressed by recruited immune cells and are induced in epithelial cells during infection. Although the mechanisms of bacterial killing by cathelicidins have been largely elucidated in vitro, those that regulate their activities in vivo are less well understood. Bacterial pathogens often co-opt host extracellular matrix (ECM) components and their functions to escape host defense; however, it is unclear whether such mechanisms exist against cathelicidins. Several studies have demonstrated that host heparan sulfate (HS) inhibits LL-37, the human cathelicidin, suggesting that bacteria might exploit HS to evade killing by cathelicidins. However, precisely how HS inhibits LL-37 and possibly other cathelicidins remains unknown, and the role of the HS-cathelicidin interaction in infectious disease has not been rigorously studied. Here, we found that deleting CRAMP, the murine cathelicidin, significantly increases the susceptibility of mice to