title: The antimicrobial peptide hLF1-11 drives monocyte-dendritic cell differentiation toward dendritic cells that promote antifungal responses and enhance Th17 polarization.
abstract: The hLF1-11 peptide comprising the first 11 N-terminal residues of human lactoferrin exerts antimicrobial activity in vivo, enhances the inflammatory response of monocytes and directs monocyte-macrophage differentiation toward cells with enhanced antimicrobial properties. In this study, we investigated the effects of hLF1-11 on human monocyte-dendritic cell (DC) differentiation and subsequent T cell activation. Results revealed that - compared to control (peptide-incubated) DCs - hLF1-11-differentiated DCs displayed enhanced expression of HLA class II antigens and dectin-1, and increased phagocytosis of Candida albicans. In addition, hLF1-11-differentiated DCs produced enhanced amounts of reactive oxygen species, IL-6 and IL-10, but not IL-12p40 and TNF-α, upon stimulation with C. albicans. Moreover, 6-day-cultured hLF1-11-differentiated DCs and control (peptide-incubated) DCs that had been stimulated with a Th17-inducing mix of antigens (including C. albicans) for 24 h were cocultured with autologous CD4+ T cells for 72 h and then the levels of IL-10, IL-17 and IFN-γ production and the percentage of cytokine-producing T cells were assessed. The results revealed that the hLF1-11-differentiated DCs induced an enhanced IL-17, but reduced IFN-γ, production by T cells as compared to control (peptide-incubated) DCs. Collectively, the hLF1-11 peptide drives monocyte-DC differentiation toward DCs that promote antifungal responses and enhance Th17 polarization.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anne M
authors.initials: AM
authors.lastname: van der Does
authors.forename: Simone A
authors.initials: SA
authors.lastname: Joosten
authors.forename: Evy
authors.initials: E
authors.lastname: Vroomans
authors.forename: Sylvia J P
authors.initials: SJ
authors.lastname: Bogaards
authors.forename: Krista E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nibbering
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000946:Antigens, Fungal / Q000276:immunology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007114:Immunization; D007781:Lactoferrin / Q000737:chemistry / Q000494:pharmacology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D000942:Antigens, Bacterial; D015703:Antigens, CD; D000946:Antigens, Fungal; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D010446:Peptide Fragments; D007781:Lactoferrin