Modulation of human β-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

Early in infection, influenza, HSV‐1 and Sendai virus modulate hBD‐1 in human plasmacytoid dendritic cells, monocytes and epithelial cells, suggesting importance in innate immunity. 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.