Impact of LL-37 of anti-infective immunity

Abstract: Host defense peptides (often called cat-ionic antimicrobial peptides) have pleiotropic im-munomodulatory functions. The human host de-fense peptide LL-37 is up-regulated at sites of in-fection and has little or no antimicrobial activity in tissue-culture media but under the same condi-tions, demonstrates immunomodulatory effects on epithelial cells, monocytes, and dendritic cells (DC). These effects include the induction of che-mokine production in a mitogen-activated protein kinase-dependent manner in epithelial cell lines and monocytes and profound alterations of DC differentiation, resulting in the capacity to enhance a T helper cell type 1 response. Although the exact mechanisms of interaction between LL-37 and these cell types have not been elucidated, there is evidence for specific (i.e., receptor-mediated) and nonspecific interactions. The relative significance of the direct antimicrobial activities and immuno-modulatory properties of LL-37 and other cationic host defense peptides in host defense remains un-resolved. To demonstrate that antimicrobial activ-ity was not necessarily required for the protection in vivo, model peptides were synthesized and tested for antimicrobial and immunomodulatory activi-ties. A peptide with no antimicrobial activity was found to be protective in animal models of Staph-ylococcus aureus and Salmonella infection, imply-ing that a host defense peptide can protect by ex-erting immunomodulatory properties. J. Leukoc