Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0708412 on June 15, 2009

Published online before print June 15, 2009
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(Journal of Leukocyte Biology. 2009;86:941-948.)
© 2009 Society for Leukocyte Biology

Human defensins activate monocyte-derived dendritic cells, promote the production of proinflammatory cytokines, and up-regulate the surface expression of CD91

Pietro Presicce*,{dagger},1, Stefania Giannelli*, Adriano Taddeo*, Maria Luisa Villa* and Silvia Della Bella*

* Dipartimento di Scienze e Tecnologie Biomediche, Cattedra di Immunologia, Università degli Studi di Milano, Italy; and
{dagger} Division of Molecular Immunology, Cincinnati Children’s Hospital Research Foundation, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

1. Correspondence: Laboratorio di Immunologia, Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Milano, Via Fratelli Cervi, 93-20090 Segrate (MI), Italy. E-mail: pietro.presicce{at}unimi.it

ABSTRACT

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.

Key Words: antigen-presenting cells • HNP-1 • HBD-1 • chemotaxis • interleukins • allostimulatory activity