Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37)

Defensins and cathelicidins are the two major families of mammalian anti-mi crobial proteins. They contribute to host, innate, anti-microbial defense b y disrupting the integrity of the bacterial cell membrane. However, several members of the mammalian anti-microbial proteins including defensins and c athelicidins have been shown recently to have chemotactic effects on host c ells, Human neutrophil alpha -defensins are chemotactic for resting, naive CD45RA/CD4 T cells, CD8 T cells, and immature dendritic cells. Human P-defe nsins are also chemotactic for immature dendritic cells but induce the migr ation of memory CDP5RO/CD4 T T cells. In contrast, cathelicidin/LL-37 is ch emotactic for neutrophils, monocytes, and T cells but not for dendritic cel ls. Thus, these anti-microbial peptides have distinct, host-target cell spe ctra. The chemotactic activities of human beta -defensins and cathelicidin/ LL-37 are mediated by human CC chemokine receptor 6 and formyl peptide rece ptor-like 1, respectively. The capacities of defensins and cathelicidins to mobilize various types of phagocytic leukocytes, immature dendritic cells, and lymphocytes, together with their other effects such as stimulating IL- 8 production and mast cell degranulation, provide evidence for their partic ipation in alerting, mobilizing, and amplifying innate and adaptive anti-mi crobial immunity of the host,