Bovine Respiratory Syncytial Virus Decreased Pasteurella multocida Adherence by Downregulating the Expression of Intercellular Adhesion Molecule-1 on the Surface of Upper Respiratory Epithelial Cells

Abstract

The synergistic infection of bovine respiratory syncytial virus (BRSV) and Pasteurella multocida (PM) may predispose cattle to develop severe pneumonia. Previously, we reported that BRSV infection significantly decreased PM adherence to the upper respiratory epithelial cells. It may allow bacteria to invade into the lower respiratory tract and lead to severe pneumonia. 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 decreased the expression of intercellular adhesion molecule-1 (ICAM1) on bTECs. Inhibition and knockdown experiments using anti-ICAM1 antibody and siRNAs targeting ICAM1 indicated that PM adherence to bTECs was dependent on ICAM1 expression. These data suggest that under normal conditions bTECs may capture PM in the upper respiratory tract, while BRSV infection reverses this mechanism. 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.

Bovine Respiratory Syncytial Virus Enhances the Adherence of Pasteurella multocida to Bovine Lower Respiratory Tract Epithelial Cells by Upregulating the Platelet-Activating Factor Receptor

“…By capturing microbes, ICAM-1 displayed by cells of the upper respiratory tract acts as a "gateway" that impedes bacterial invasion of the lower respiratory tract (Sudaryatma et al, 2020). BRSV infection causes malfunction of ICAM-1 in the bovine upper respiratory tract, allowing bacterial invasion of the lower respiratory tract (Sudaryatma et al, 2020). The results of the present study demonstrated that BRSV infection increased PAFR expression in epithelial cells derived from the lower respiratory tract.…”

“…In recent work (Sudaryatma et al, 2020), we have obtained evidence suggesting that the upper respiratory tract is responsible for inhibiting PM invasion of the lower respiratory tract. This inhibition is accomplished by trapping PM via ICAM-1, an adherence molecule that is displayed on the cellular surface under normal conditions.…”

“…This inhibition is accomplished by trapping PM via ICAM-1, an adherence molecule that is displayed on the cellular surface under normal conditions. By capturing microbes, ICAM-1 displayed by cells of the upper respiratory tract acts as a "gateway" that impedes bacterial invasion of the lower respiratory tract (Sudaryatma et al, 2020). BRSV infection causes malfunction of ICAM-1 in the bovine upper respiratory tract, allowing bacterial invasion of the lower respiratory tract (Sudaryatma et al, 2020).…”

“… Schematic model of the synergistic effect of coinfection by bovine respiratory syncytial virus (BRSV) and Pasteurella multocida (PM) in cattle with severe pneumonia. Epithelial cells in the upper respiratory tract (trachea) capture PM via intercellular adhesion molecule-1 (ICAM-1) under normal conditions and serve as a biological gateway ( Sudaryatma et al, 2020 ). BRSV infection abrogates this gateway function by downregulating ICAM-1 on the epithelial cells of the upper respiratory tract and upregulating the platelet-activating factor receptor (PAFR) on the epithelial cells of the lower respiratory tract.…”

Bovine respiratory coronavirus enhances bacterial adherence by upregulating expression of cellular receptors on bovine respiratory epithelial cells

“…Interestingly, the number of adhering bacteria decreased and increased in BRSV-infected cells derived from the upper and lower respiratory tract, respectively. These changes in the number of adhering bacteria were caused by down- and upregulation, respectively, of two bacterial adhesion molecules ( Sudaryatma et al, 2020a , 2020b ). Reduced and enhanced bacterial adherence to BRSV-infected upper and lower BRECs would permit bacteria to pass from the upper to lower respiratory tract, inducing severe pneumonia.…”