title: The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands.
abstract: The endogenous anti-microbial peptide LL-37/hCAP-18 is an effector molecule of the innate host defense system at surfaces of the body. Besides its direct anti-microbial activity, the peptide interacts with different cell types. Dendritic cells (DCs) play a central role in mucosal host defense. It was the aim of the study to determine whether LL-37 modulates the response of DCs to pathogen-associated molecular patterns. Monocyte-derived DCs were stimulated with the Toll-like receptors (TLRs) ligands LPS, lipoteichoic acid and flagellin. We measured classical markers of DC maturation and assayed the ability of the DCs to activate T cell responses. Co-incubation with LL-37 resulted in suppressed activation of DCs. Levels of released IL-6, IL-12p70 and TNF-alpha and surface expression of HLA-DR, CD80, CD83, CD86 and the chemokine receptor CCR7 were decreased. Exposure of DCs to LL-37 during LPS exposure induced co-cultured naive T cells to produce less IL-2 and IFN-gamma and decreased their proliferation. The response of memory T cells to a recall antigen was also decreased. In conclusion, we demonstrate that the anti-microbial peptide LL-37 inhibits the activation of DCs by TLR ligands. We propose that LL-37 is a regulator of host defense responses at the intersection of innate and adaptive immune systems.
authors.affiliation: Department of Internal Medicine, Division for Pulmonary Diseases, Baldingerstrasse 1, 35043 Marburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kandler
authors.forename: Renat
authors.initials: R
authors.lastname: Shaykhiev
authors.forename: Peter
authors.initials: P
authors.lastname: Kleemann
authors.forename: Frank
authors.initials: F
authors.lastname: Klescz
authors.forename: Michael
authors.initials: M
authors.lastname: Lohoff
authors.forename: Claus
authors.initials: C
authors.lastname: Vogelmeier
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D008024:Ligands; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D054804:Cathelicidins