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

Pietro Presicce, Stefania Giannelli, Adriano Taddeo, Maria Luisa Villa, Silvia Della Bella

Research output: Contribution to journalArticle

70 Citations (Scopus)

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 α-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-α, 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.

Original languageEnglish
Pages (from-to)941-948
Number of pages8
JournalJournal of Leukocyte Biology
Volume86
Issue number4
DOIs
Publication statusPublished - Oct 2009

Fingerprint

Defensins
Dendritic Cells
Monocytes
Up-Regulation
Cytokines
Adaptive Immunity
Innate Immunity
Scavenger Receptors
HLA-DR Antigens
Interleukin-10
Immunity
Interleukin-6
Parasites
Fungi
human neutrophil peptide 1
Ligands
Viruses
Bacteria
Peptides

Keywords

  • Allostimulatory activity
  • Antigen-presenting cells
  • Chemotaxis
  • HBD-1
  • HNP-1
  • Interleukins

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Human defensins activate monocyte-derived dendritic cells, promote the production of proinflammatory cytokines, and up-regulate the surface expression of CD91. / Presicce, Pietro; Giannelli, Stefania; Taddeo, Adriano; Villa, Maria Luisa; Della Bella, Silvia.

In: Journal of Leukocyte Biology, Vol. 86, No. 4, 10.2009, p. 941-948.

Research output: Contribution to journalArticle

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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 α-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-α, 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.",
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