Modulation of human beta-defensin-1 (hBD-1) in plasmacytoid dendritic cells (PDC), monocytes, and epithelial cells by influenza virus, Herpes simplex virus, and Sendai virus and its possible role in innate immunity

J Leukoc Biol. 2011 Aug;90(2):343-56. doi: 10.1189/jlb.0209079. Epub 2011 May 6.


hBD comprise a family of antimicrobial peptides that plays a role in bridging the innate and adaptive immune responses to infection. The expression of hBD-2 increases upon stimulation of numerous cell types with LPS and proinflammatory cytokines. In contrast, hBD-1 remains constitutively expressed in most cells in spite of cytokine or LPS stimulation; however, its presence in human PDC suggests it plays a role in viral host defense. To examine this, we characterized the expression of hBD-1 in innate immune cells in response to viral challenge. PDC and monocytes increased production of hBD-1 peptide and mRNA as early as 2 h following infection of purified cells and PBMCs with PR8, HSV-1, and Sendai virus. However, treatment of primary NHBE cells with influenza resulted in a 50% decrease in hBD-1 mRNA levels, as measured by qRT-PCR at 3 h following infection. A similar inhibition occurred with HSV-1 challenge of human gingival epithelial cells. Studies with HSV-1 showed that replication occurred in epithelial cells but not in PDC. Together, these results suggest that hBD-1 may play a role in preventing viral replication in immune cells. To test this, we infected C57BL/6 WT mice and mBD-1((-/-)) mice with mouse-adapted HK18 (300 PFU/mouse). mBD-1((-/-)) mice lost weight earlier and died sooner than WT mice (P=0.0276), suggesting that BD-1 plays a role in early innate immune responses against influenza in vivo. However, lung virus titers were equal between the two mouse strains. Histopathology showed a greater inflammatory influx in the lungs of mBD-1((-/-)) mice at Day 3 postinfection compared with WT C57BL/6 mice. The results suggest that BD-1 protects mice from influenza pathogenesis with a mechanism other than inhibition of viral replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Humans
  • Immunity, Innate*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / virology
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae Infections / immunology
  • RNA Viruses / immunology*
  • Sendai virus / immunology
  • Simplexvirus / immunology
  • beta-Defensins / deficiency
  • beta-Defensins / immunology*
  • beta-Defensins / metabolism


  • DEFB1 protein, human
  • Defb1 protein, mouse
  • beta-Defensins