title: 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.
abstract: 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.
authors.affiliation: The Public Health Research Institute and Department of Medicine, Division of Pulmonary and Critical Care Medicine, New Jersey Medical School, Newark, NJ 07103, USA. ryanlk@umdnj.edu
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Ryan
authors.forename: Jihong
authors.initials: J
authors.lastname: Dai
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Yin
authors.forename: Nicholas
authors.initials: N
authors.lastname: Megjugorac
authors.forename: Victoria
authors.initials: V
authors.lastname: Uhlhorn
authors.forename: Sunghan
authors.initials: S
authors.lastname: Yim
authors.forename: Kyell D
authors.initials: KD
authors.lastname: Schwartz
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Abrahams
authors.forename: Gill
authors.initials: G
authors.lastname: Diamond
authors.forename: Patricia
authors.initials: P
authors.lastname: Fitzgerald-Bocarsly
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology; D012328:RNA Viruses / Q000276:immunology*; D029082:Sendai virus / Q000276:immunology; D018139:Simplexvirus / Q000276:immunology; D023083:beta-Defensins / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism
chemical_list: C406407:DEFB1 protein, human; C120555:Defb1 protein, mouse; D023083:beta-Defensins