Lipopolysaccharides (LPS) from gut commensal bacteria trigger immunomodulatory responses on the basis of their structures. However, only a few gut commensal LPS have been structurally elucidated so far. Therefore, the molecular motifs crucial for LPS−host interactions at the gut level remain obscure. In this communication, I will focus on the LPS of two commensals of the human intestine: Bacteroides vulgatus and Alcaligenes faecalis. I will show that B. vulgatus LPS does not induce proinflammatory cytokines release and that its administration is enough to reestablish intestinal immune homeostasis in a mouse model for experimental colitis. I will also present that the LPS structural characterization revealed an unprecedented structure based on a hypo-acylated and mono-phosphorylated lipid A, a galactofuranose-containing core OS, and an O-antigen built up of mannose and rhamnose. To this particular structure corresponds an intriguing ability, in human in vitro models, to produce antiinflammatory cytokines and to induce the synergistic activation of TLR4- and TLR2-mediated signaling pathways. As for A. faecalis, this is the sole Gram-negative inhabiting gut lymphoid tissues, Peyer’s patches (PPs), which are the largest sites for the initiation and regulation of intestinal IgA responses. We already showed that Alcaligenes LPS maintain a homeostatic environment in PPs, without triggering any harmful response. Acting as such, this LPS would take part in the host immune vigilance through the production of IgA, which in turn might favor their persistence in PPs. Here I will highlight that also A. faecalis LPS has an unreported structure with a mono-phosphorylated core OS, which contains a huge number of N-acetyl hexosamines. The O-antigen is a xylosylated rhamnan chain while the lipid A is a mixture of tetra- to hexa-acylated species. Finally, I will show that these differently acylated lipid A have been synthesized and their immunological properties tested, revealing that only the hexa-acylated one is able to induce NF-κB activation in TLR4-expressing cells, which was however weaker than upon stimulation by E. coli LPS.

Koichi Fukase

Appearances