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-microbial proteins. They contribute to host, innate, anti-microbial defense by disrupting the integrity of the bacterial cell membrane. However, several members of the mammalian anti-microbial proteins including defensins and cathelicidins have been shown recently to have chemotactic effects on host cells. Human neutrophil alpha-defensins are chemotactic for resting, naïve CD45RA/CD4 T cells, CD8 T cells, and immature dendritic cells. Human beta-defensins are also chemotactic for immature dendritic cells but induce the migration of memory CD45RO/CD4 T cells. In contrast, cathelicidin/LL-37 is chemotactic for neutrophils, monocytes, and T cells but not for dendritic cells. Thus, these anti-microbial peptides have distinct, host-target cell spectra. The chemotactic activities of human beta-defensins and cathelicidin/LL-37 are mediated by human CC chemokine receptor 6 and formyl peptide receptor-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 participation in alerting, mobilizing, and amplifying innate and adaptive anti-microbial immunity of the host.
Yang
D
D
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, USA.
Chertov
O
O
Oppenheim
J J
JJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology* / Q000378:metabolism; D000890:Anti-Infective Agents / Q000276:immunology* / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D054804:Cathelicidins; D023082:Defensins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008322:Mammals; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054804:Cathelicidins; D023082:Defensins; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide