Human defensins activate monocyte-derived dendritic cells, promote the production of proinflammatory cytokines, and up-regulate the surface expression of CD91.
Defensins are endogenous defense peptides with well defined antimicrobial activity against a broad spectrum of pathogens including bacteria, fungi, viruses, and parasites.Several lines of evidence suggest that defensins might also contribute to the regulation of host innate and adaptive immunity, but their immunomodulatory functions are still poorly understood. Herein, we studied the impact of human defensins on multiple functions of DCs, which are a central player in all immune responses, bridging innate and adaptive immunity. We challenged DCs differentiated in vitro from human moDCs with HNP-1 alpha-defensin or HBD-1. HNP-1 and HBD-1 were chemotactic for moDCs. Both defensins promoted the activation and maturation of moDCs, as assessed by up-regulation of surface expression of the costimulatory molecules CD80, CD86, and CD40, the maturation marker CD83, and HLA-DR. HNP-1 and HBD-1 also enhanced the production of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12p70 but did not affect the production of the regulatory cytokine IL-10. According to these stimulatory effects, HNP-1 and HBD-1 increased the allostimulatory activity of moDCs significantly. Finally, HNP-1 and HBD-1 promoted the up-regulation of CD91 on the DC surface. CD91 is a scavenger receptor involved in the recognition of multiple ligands including defensins, thus suggesting that defensins may amplify their own effects through the activation of an autocrine loop. Taken together, our observations may provide new insight into the immunomodulatory properties of human defensins and may aid the exploration of new therapeutic strategies to potentiate antimicrobial and antitumor immunity.
Presicce
Pietro
P
Dipartimento di Scienze e Tecnologie Biomediche, Cattedra di Immunologia, Università degli Studi di Milano, 93-20090 Segrate (MI), Italy. pietro.presicce@unimi.it
Giannelli
Stefania
S
Taddeo
Adriano
A
Villa
Maria Luisa
ML
Della Bella
Silvia
S
D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D023082:Defensins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D016207:Cytokines; D023082:Defensins; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1