Antimicrobial peptide LL-37 internalized by immature human dendritic cells alters their phenotype.
The human cathelicidin LL-37 has been shown to be involved in the barrier function of the innate immunity, being released from specific cells upon challenge and exerting immunomodulatory effects. We here demonstrate that LL-37 affects immature dendritic cells, derived from human peripheral blood monocytes (MDDC). LL-37 is internalized by MDDC with subsequent localization primarily in the cytoplasmic compartment. However, LL-37 could also be detected in the nuclei of MDDC, suggesting that LL-37 may be transported into the nucleus. The uptake of LL-37 is dose, time and energy dependent, indicating that the observed internalization process involves an endocytic pathway. Incubation of immature MDDC with LL-37 caused phenotypic changes, characterized by an increased expression of the antigen-presenting molecule HLA-DR, and the costimulatory molecule CD86. Taken together, these findings suggest that LL-37 released upon triggering of the innate immunity, may affect cellular adaptive immunity through an interaction with immature dendritic cells.
Bandholtz
L
L
Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Ekman
G Jacobsson
GJ
Vilhelmsson
M
M
Buentke
E
E
Agerberth
B
B
Scheynius
A
A
Gudmundsson
G H
GH
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D054804:Cathelicidins