Bacteroides thetaiotaomicron rough-type lipopolysaccharide: The chemical structure and the immunological activity

Bacteroides thetaiotaomicron is one of the most extensively studied symbionts of the human gut. Despite its widespread distribution among human populations, still very little is known about the role of its cell envelope in the crosstalk with the immune system. Due to the extraordinary characteristic of B. thetaiotaomicron to express multiple capsular polysaccharides on its surface, research activities focused on defining how these polymers affect immune responses. This resulted in the drawback of neglecting another immunostimulatory cell surface glycoconjugate, the lipopolysaccharide (LPS). By taking advantage of an acapsular mutant of B. thetaiotaomicron , here we describe the characterization of the structure of the rough-type LPS produced by this gut mutualist. This was made up of a mono -phosphorylated and hypoacylated lipid A and of a highly charged core oligosaccharide. In vitro studies revealed a weak ability to engage the MD-2/TLR4 pathway, while it was able to promote TLR2-mediated response. • Bacteroides thetaiotaomicron ( B. thetaiotaomicron ) is a Gram-negative gut bacterium key for the intestinal epithelium and immunological development. • B. thetaiotaomicron expresses multiple capsular polysaccharides on its surface. This hindered the proper isolation and characterization of its lipopolysaccharide (LPS) constituent. • An acapsular mutant of B. thetaiotaomicron showed to express a rough-type LPS (R-LPS) made up of a mono -phosphorylated and hypoacylated lipid A and of a highly charged core oligosaccharide. • B. thetaiotaomicron R-LPS showed a weak ability to engage the MD-2/TLR4 pathway, while it was able to activate TLR2-mediated response. • A differential cytokine release profile upon stimulation with B. thetaiotaomicron R-LPS of HEK293 cells transfected with TLR2 or TLR4 genes was observed.