A CASE OF ECTOPIA CORDIS
摘要
Although BPIFA1 is one of the most abundant secretory proteins in the upper airways, its9 function remains unclear. We have recently shown a reduction of BPIFA1 in the airways following influenza-A virus infection. In the present study we evaluated the host defence role of BPIFA1 in viral respiratory infection using an <i>in vitro</i> tracheal model. Tracheal epithelial cells isolated from wild-type and <i>bpifa<sup>-/-</sup></i> mice, were seeded onto transwells and differentiated in ALI culture. Differentiated epithelium was infected with influenza-A virus (H3N2). Samples were collected at 2, 24, 48 and 72 hpi (hours post infection). Our data shows that the differentiated epithelial layer mimics the original tracheal epithelium, and abundant BPIFA1 was detected in the apical secretions and cytoplasm of differentiated epithelium. Influenza-A infection initiated inflammatory gene expression, where, IL-6 (2 hpi), TNF-α, IFN-β and IFN-λ2 (24 hpi) were highly upregulated. Influenza-A primarily infected ciliated cells, these cells then lost physical cilia and they down-regulated ciliated gene expression. At low dose (MOI-0.1), BPIFA1 and MUC5B expressing cells were largely uninfected. However, at high dose (MOI-0.5), BPIFA1 +ve cells were also infected and BPIFA1 was down-regulated 6-fold within 48 hpi. At 24 and 48 hpi, viral load was 2.3-fold higher in <i>bpifa<sup>-/-</sup></i> cells with these cells exhibiting increased cell death compared to wild-type cell cultures. Our data suggest that BPIFA1 abrogates influenza-A viral infection and therefore, can be a novel target for antiviral treatment for respiratory tract infections.