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

Abstract

Coinfection by bovine respiratory syncytial virus (BRSV) and Pasteurella multocida (PM) frequently has been observed in cattle that develop severe pneumonia. We recently reported that BRSV infection significantly increased PM adherence to bovine lower respiratory tract epithelial cells. However, the molecular mechanisms of enhanced PM adherence are not completely understood. To investigate whether BRSV infection regulates any cellular adherence receptors on bovine bronchus-and lung-epithelial cells, we performed proteomic and functional analyses. The proteomic analysis showed that BRSV infection increased the accumulation of the platelet-activating factor receptor (PAFR) in both cell types. Molecular experiments, including specific blockade, knockdown, and overexpression of PAFR, indicated that PM adherence to these cell types depended on PAFR expression. These findings highlight the role, in cattle with severe pneumonia, of the synergistic effect of coinfection by BRSV and PM in the lower respiratory tract.

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

“…We recently demonstrated that expression of two cell surface receptors, platelet-activating factor receptor (PAF-R) and intercellular adhesion molecule-1 (ICAM-1), determines the adherence of PM to BRSV-infected BRECs ( Sudaryatma et al, 2020a , 2020b ). Based on this finding, we measured the expression levels of these receptors by qRT-PCR and western blotting.…”

“…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.…”

Bovine respiratory microbiota of feedlot cattle and its association with disease

“…The presence of viruses in the bovine respiratory tract may also alter the microenvironment of mucosal surfaces and bacterial structure, leading to reduced mucociliary function and cilia damage. Additionally, viral infection could reduce the concentration of antimicrobial peptides, bacterial adherence and invasion by adjusting the host immune system [ 129 ]. Segal et al [ 130 ] observed that enhanced expression of inflammatory cytokines (Th17 immune activation) is associated with bacteria in the human LRT, which indicates that the respiratory microbiota could regulate the inflammatory condition at the mucosal surface in humans.…”

Understanding the mechanisms of viral and bacterial coinfections in bovine respiratory disease: a comprehensive literature review of experimental evidence

“…The authors noticed that P. multocida adherence was greatly increased in pre-infected cells derived from the lower respiratory tract compared to cells that were not previously exposed to BRSV, together with an up-regulation of IL-6 mRNA expression. The same authors later reported an increased accumulation of the platelet-activating factor receptor (PAFR) in vitro and also demonstrated that P. multocida adherence depended on PAFR expression [ 133 ]. This work highlights a possible mechanism of bacterial superinfection caused by P. multocida following BRSV infection, that is often observed in field conditions [ 8 ].…”