Cathelicidins are multifunctional cationic host-defence
peptides (CHDP; also known as
antimicrobial peptides) and an important component of innate host defence against
infection. In addition to microbicidal potential, these
peptides have properties with the capacity to modulate
inflammation and immunity. However, the extent to which such properties play a significant role during
infection in vivo has remained unclear. A murine model of acute P. aeruginosa lung
infection was utilised, demonstrating
cathelicidin-mediated enhancement of bacterial clearance in vivo. The delivery of exogenous synthetic human
cathelicidin LL-37 was found to enhance a protective pro-inflammatory response to
infection, effectively promoting bacterial clearance from the lung in the absence of direct microbicidal activity, with an enhanced early neutrophil response that required both
infection and
peptide exposure and was independent of native
cathelicidin production. Furthermore, although
cathelicidin-deficient mice had an intact early cellular inflammatory response, later phase neutrophil response to
infection was absent in these animals, with significantly impaired clearance of P. aeruginosa. These findings demonstrate the importance of the modulatory properties of
cathelicidins in pulmonary
infection in vivo and highlight a key role for
cathelicidins in the induction of protective pulmonary neutrophil responses, specific to the infectious milieu. In additional to their physiological roles, CHDP have been proposed as future antimicrobial
therapeutics. Elucidating and utilising the modulatory properties of
cathelicidins has the potential to inform the development of synthetic
peptide analogues and novel therapeutic approaches based on enhancing innate host defence against
infection with or without direct microbicidal targeting of pathogens.