Modulation of phenotype and function of dendritic cells by a therapeutic synthetic killer peptide.
The strong microbicidal effects of an engineered synthetic killer peptide (KP), which functionally mimics a fungal killer toxin, have been demonstrated extensively. Beta-glucan has been identified as a receptor for KP on fungal cell walls. Although the direct microbicidal and related therapeutic effects have been studied in depth, no information currently exists about the interaction of KP with immune cells. In this study, we exploited the possibility of KP binding to different murine immune cell populations. The results demonstrate that KP binds selectively to dendritic cells (DC) and to a lesser extent, to macrophages but not to lymphocytes and neutrophils; KP binding possibly occurs through major histocompatibility complex (MHC) class II, CD16/32, and cellular molecules recognized by anti-specific intercellular adhesion molecule-grabbing nonintegrin R1 antibodies; and KP modulates the expression of costimulatory and MHC molecules on DC and improves their capacity to induce lymphocyte proliferation. These findings provide evidence that this synthetic KP interacts selectively with DC and modulating their multiple functions, might also serve to improve the immune antimicrobial response.
Cenci
Elio
E
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Pericolini
Eva
E
Mencacci
Antonella
A
Conti
Stefania
S
Magliani
Walter
W
Bistoni
Francesco
F
Polonelli
Luciano
L
Vecchiarelli
Anna
A
D000818:Animals; D000935:Antifungal Agents / Q000276:immunology / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009181:Mycoses / Q000188:drug therapy / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology / Q000494:pharmacology*; D017452:Receptors, IgG / Q000276:immunology; D047071:beta-Glucans / Q000276:immunology
D000935:Antifungal Agents; D000949:Histocompatibility Antigens Class II; D009842:Oligopeptides; D017452:Receptors, IgG; D047071:beta-Glucans