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

Abstract

Alcaligenes are 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 (Alcaligenes LPS) 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 Alcaligenes LPS was weaker than that of Escherichia coli-derived LPS and therefore no excessive inflammation was induced by Alcaligenes LPS in vitro or in vivo. Alcaligenes LPS 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 Alcaligenes LPS could be a safe and potent adjuvant.

• Authors: Naoko Shibata, Jun Kunisawa, Koji Hosomi, Yukari Fujimoto, Keisuke Mizote, Naohiro Kitayama, Atsushi Shimoyama, Hitomi Mimuro, Shintaro Sato, Natsuko Kishishita, Ken J Ishii, Koichi Fukase, Hiroshi Kiyono
• Journal: Mucosal immunology (Mucosal Immunol) Vol. 11 Issue 3 Pg. 693-702 (05 2018) ISSN: 1935-3456 [Electronic] United States
• PMID: 29411777 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Immunoglobulin A
• Interleukin-6
• Lipopolysaccharides
• Tlr4 protein, mouse
• Toll-Like Receptor 4

Topics

• Adjuvants, Immunologic
• Alcaligenes (immunology)
• Animals
• Antibody Formation
• Cells, Cultured
• Dendritic Cells (immunology)
• Gram-Negative Bacterial Infections (immunology)
• Homeostasis
• Immunoglobulin A (metabolism)
• Inflammation (immunology)
• Interleukin-6 (metabolism)
• Lipopolysaccharides (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Toll-Like Receptor 4 (agonists)