Lymphoid tissue-resident AlcaligenesLPS induces IgA production without excessive inflammatory responses via weak TLR4 agonist activity

Alcaligenesare opportunistic commensal bacteria that reside in gut-associated lymphoid tissues such as Peyer’s patches (PPs); however, how they create and maintain their homeostatic environment, without inducing an excessive inflammatory response remained unclear. We show here that Alcaligenes-derived lipopolysaccharide (AlcaligenesLPS) acts as a weak agonist of toll-like receptor 4 and promotes IL-6 production from dendritic cells, which consequently enhances IgA production. The inflammatory activity of AlcaligenesLPS was weaker than that of Escherichia coli-derived LPS and therefore no excessive inflammation was induced by AlcaligenesLPS in vitroor in vivo. AlcaligenesLPS also showed adjuvanticity, inducing antigen-specific immune responses without excessive inflammation. These findings reveal the presence of commensal bacteria-mediated homeostatic inflammatory conditions within PPs that produce optimal IgA induction without causing pathogenic inflammation and suggest that AlcaligenesLPS could be a safe and potent adjuvant.