The anti-microbial peptide LL-37 modulates immune responses in the palatine tonsils where it is exclusively expressed by neutrophils and a subset of dendritic cells.
Antimicrobial peptides are essential elements of epithelial defense against invading micro-organisms. The palatine tonsils are positioned at the entry of the airway and the gut and as such are ideally situated to act as immune sentinels in the pharynx protecting against microbial invasion. Tonsils express a number of antimicrobial peptides including hCAP18/LL-37. Here we clearly define the expression of hCAP18/LL-37 in the tonsils showing unequivocally that hCAP18/LL-37 is mainly expressed by infiltrating neutrophils and follicular CD11c+CD13+HLA-DR+ dendritic cells, rarely by macrophages, and never by the epithelium itself. To explore possible functions for follicle-derived LL-37, we stimulated tonsil mononuclear cells with LL-37 in vitro and observed the secretion of the proinflammatory cytokines CCL5 and CXCL9, expression of IFN-γ and MX-1 and down-regulation of chemokine receptors CCR4 and CCR6 which are involved in tissue-selective T cell trafficking. Taken together, these data illustrate new potential immunoregulatory functions for hCAP18/LL-37 in the tonsils.
Department of Immunology, Landspitali-University Hospital, Reykjavik, Iceland.
Sigrun L
SL
Sigurdardottir
Ragna H
RH
Thorleifsdottir
Andrew M
AM
Guzman
Gudmundur H
GH
Gudmundsson
Helgi
H
Valdimarsson
Andrew
A
Johnston
D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism; D054365:Chemokine CXCL5 / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation; D004848:Epithelium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D064547:Myxovirus Resistance Proteins; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D014066:Palatine Tonsil / Q000276:immunology* / Q000378:metabolism; D054398:Receptors, CCR4 / Q000378:metabolism; D054399:Receptors, CCR6 / Q000378:metabolism; D015854:Up-Regulation; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; C515354:CCR4 protein, human; C106311:CCR6 protein, human; C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D054370:Chemokine CXCL9; D064547:Myxovirus Resistance Proteins; D054398:Receptors, CCR4; D054399:Receptors, CCR6; D007371:Interferon-gamma; D019204:GTP-Binding Proteins; D054804:Cathelicidins