Sialylated Lipooligosaccharide Contributes to Glaesserella parasuis Penetration of Porcine Respiratory Epithelial Barrier

Pathogens utilize various mechanisms to escape host immunological surveillance, break down different tissue barriers, and cause infection. Sialylation is an important surface modification of bacterial outer membrane components, especially the lipooligosaccharide of Gram-negative bacteria. It is widely involved in multiple microbe-host interactions, such as bacterial virulence regulation, host recognition, and immune evasion. There are some sialylation modifications on the lipooligosaccharide structure of Glaesserella parasuis (G. parasuis) virulent strains. However, the role of lipooligosaccharide sialylation modification in the process of G. parasuis infection and penetration of the porcine respiratory epithelial barrier is still unclear. In this study, we investigated the role and mechanism of lsgB-mediated lipooligosaccharide sialylation in G. parasuis invasion of the host respiratory epithelial barrier. Specifically, G. parasuis lsgB-mediated lipooligosaccharide sialylation and sialylated-lipooligosaccharide interacted with Siglec1 on porcine alveolar macrophages 3D4/21 and triggered the subsequent generation of TGFβ1 through Siglec1/Dap12/Syk/p38 signaling cascade. TGFβ1 decreased the tracheal epithelial tight junctions and the expression of extracellular adhesion molecule fibronectin, thus assisting G. parasuis invasion and entry to the respiratory epithelial barrier. Characterizing the potential effects and mechanisms of lipooligosaccharide sialylation-mediated TGFβ1 production would further expand our current knowledge on the pathogenesis of G. parasuis which will contribute to better prevention and control of G. parasuis infection in piglets.