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Comprehensive Study of Co-infection Virus and Bacteria In the Epithelial Cells
Bovine respiratory disease complex is a major disease affecting the global cattle industry. Multiple infections by viruses and bacteria increase disease severity. In this studies, we reported that bovine respiratory syncytial virus (BRSV) infection increases adherence of Pasteurella multocida to human respiratory and bovine kidney epithelial cells. To examine the interaction between the virus and bacteria in bovine respiratory cells, we generated respiratory epithelial cell lines from bovine trachea (bTEC), bronchus (bBEC), and lung (bLEC). Although all established cell lines were infected by BRSV and P. multocida susceptibility differed according to site of origin. The cells derived from the lower respiratory tract (bBEC and bLEC) were significantly more susceptible to BRSV than those derived from the upper respiratory tract (bTEC). Pre- infection of bBEC and bLEC with BRSV increased adherence of Pasteurella multocida; this was not the case for bTEC. To investigate whether BRSV infection regulates the cell surface adherence receptor on bovine trachea epithelial cells (bTECs), we performed proteomic and functional analyses. BRSV infection. Inhibition and knockdown experiments using anti-ICAM1 antibody and siRNAs targeting ICAMI indicated that PM adherence to bTECs was dependent on ICAM1 expression. The proteomic analysis showed that BRSV infection decreased the expression of intercellular adhesion molecule-1 (ICAM1) on bTECs and increased the accumulation of the platelet-activating factor receptor (PAFR) in bBECs and bLECs. Molecular experiments, including specific blockade, knockdown, and overexpression of PAFR, indicated that PM adherence to these cell types depended on surface receptors expression. These findings highlight the role, in cattle with severe pneumonia, of the synergistic effect of coinfection by BRSV and PM from upper to lower respiratory tract. These data suggest that under normal conditions bTEC may capture PM in the upper respiratory tract, while BRSV infection reverses this mechanism and increased of cellular damaged in bLECs as a representative of lower respiratory tract. The proposed gateway function of bTECs is disrupted by BRSV infection that may facilitate bacterial invasion into the lower respiratory tract and lead to secondary or more severe respiratory infection. These results indicate that BRSV may reproduce better in the lower respiratory tract and encourage adherence of bacteria. Thus, we identify one possible mechanism underlying severe pneumonia.
B23000117 | DIS 599.735.5 PUT c | Archivelago Indonesia Marine Library - Perpustakaan Kementerian Kelautan dan Perikanan | Available |
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