A novel, complement-mediated way to enhance the interplay between macrophages, dendritic cells and T lymphocytes.
Recently it has been reported that human C3-deficiency is associated with impairments in dendritic cell differentiation. Here we investigated how complement C3 influences the phenotype and functional activity of human dendritic cells. We show that human monocyte-derived dendritic cells (MDCs) when incubated with native, hemolytically active C3, bind the activation fragments of C3 covalently. This reaction directs MDCs to increase expression of MHCII, CD83 and CD86, moreover it results in a significantly enhanced secretion of TNF-alpha, IL-6 and IL-8. A further functional consequence of C3b-fixation is the elevated capacity of the dendritic cells to stimulate allogeneic T cells. The distinct role of covalently fixed C3-fragments is strongly supported by our results obtained with MDCs where CD11b expression was downregulated by siRNA. To reveal the possible in vivo significance of the present findings we modelled a phenomenon occurring during inflammation, where C3 is produced locally by activated macrophages. In these cocultures MDCs were found to fix substantial amounts of macrophage derived C3-fragments on their cell membrane. Our data provide compelling evidence that antigen presenting cells arising in complement-sufficient environment mature to competent stimulators of T cells.
Department of Immunology, Institute of Biology, Eötvös Loránd University, Pázmány Péter sétány 1/C, Budapest H-1117, Hungary.
Noémi
N
Sándor
Domonkos
D
Pap
József
J
Prechl
Anna
A
Erdei
Zsuzsa
Z
Bajtay
D015703:Antigens, CD / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D002454:Cell Differentiation; D003179:Complement C3b / Q000276:immunology; D003168:Complement Fixation Tests; D003165:Complement System Proteins / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D003179:Complement C3b; D003165:Complement System Proteins; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen