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
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
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DOI：
10.1189/jlb.0209079
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发表时间：
2011-08-01
影响因子：
5.5
通讯作者：
Fitzgerald-Bocarsly, Patricia
中科院分区：
文献类型：
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作者：
Ryan, Lisa K.;Dai, Jihong;Fitzgerald-Bocarsly, Patricia
hBD包含一个抗菌肽家族，在连接感染的先天和适应性免疫反应中起作用。在LPS和促炎细胞因子刺激多种细胞类型后，hBD-2的表达增加。相比之下，尽管受到细胞因子或LPS刺激，hBD-1仍在大多数细胞中组成性表达；然而，它在人类PDC中的存在表明它在病毒宿主防御中起作用。为了检验这一点，我们表征了hBD-1在应对病毒攻击的先天免疫细胞中的表达。早在PR8、HSV-1和仙台病毒感染纯化细胞和pbmc后2小时，PDC和单核细胞就增加了hBD-1肽和mRNA的产生。然而，用流感处理原代NHBE细胞导致hBD-1 mRNA水平在感染后3小时通过qRT-PCR测量下降50%。HSV-1对人牙龈上皮细胞的攻击也有类似的抑制作用。对HSV-1的研究表明，复制发生在上皮细胞中，而不在PDC细胞中。总之，这些结果表明，hBD-1可能在阻止免疫细胞中的病毒复制中发挥作用。为了验证这一点，我们用小鼠适应的HK18 （300 PFU/小鼠）感染了C57BL/6 WT小鼠和mBD-1（(-/-)）小鼠。mBD-1（(-/-)）小鼠比WT小鼠更早体重减轻和死亡（P=0.0276），提示BD-1在体内抗流感的早期先天免疫应答中起作用。然而，两株小鼠的肺病毒滴度相等。组织病理学显示，与WT C57BL/6小鼠相比，mBD-1（(-/-)）小鼠感染后第3天肺部炎症内流更大。结果表明，BD-1保护小鼠免受流感发病的机制不是抑制病毒复制。j . Leukoc。生物学杂志。90:343-356；2011.
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. J. Leukoc. Biol. 90: 343-356; 2011.