title: Antibody constant region peptides can display immunomodulatory activity through activation of the Dectin-1 signalling pathway.
abstract: We previously reported that a synthetic peptide with sequence identical to a CDR of a mouse monoclonal antibody specific for difucosyl human blood group A exerted an immunomodulatory activity on murine macrophages. It was therapeutic against systemic candidiasis without possessing direct candidacidal properties. Here we demonstrate that a selected peptide, N10K, putatively deriving from the enzymatic cleavage of the constant region (Fc) of human IgG(1), is able to induce IL-6 secretion and pIkB-α activation. More importantly, it causes an up-regulation of Dectin-1 expression. This leads to an increased activation of β-glucan-induced pSyk, CARD9 and pIkB-α, and an increase in the production of pro-inflammatory cytokines such as IL-6, IL-12, IL-1β and TNF-α. The increased activation of this pathway coincides with an augmented phagocytosis of non opsonized Candida albicans cells by monocytes. The findings suggest that some Fc-peptides, potentially deriving from the proteolysis of immunoglobulins, may cause an unexpected immunoregulation in a way reminiscent of innate immunity molecules.
authors.affiliation: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gabrielli
authors.forename: Eva
authors.initials: E
authors.lastname: Pericolini
authors.forename: Elio
authors.initials: E
authors.lastname: Cenci
authors.forename: Claudia
authors.initials: C
authors.lastname: Monari
authors.forename: Walter
authors.initials: W
authors.lastname: Magliani
authors.forename: Tecla
authors.initials: T
authors.lastname: Ciociola
authors.forename: Stefania
authors.initials: S
authors.lastname: Conti
authors.forename: Rita
authors.initials: R
authors.lastname: Gatti
authors.forename: Francesco
authors.initials: F
authors.lastname: Bistoni
authors.forename: Luciano
authors.initials: L
authors.lastname: Polonelli
authors.forename: Anna
authors.initials: A
authors.lastname: Vecchiarelli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans / Q000502:physiology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry*; D056747:Immunomodulation; D037181:Lectins, C-Type / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D000099181:Dectin-1
chemical_list: D007141:Immunoglobulin Fc Fragments; D037181:Lectins, C-Type; D010446:Peptide Fragments; D000099181:Dectin-1