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

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)693-702
Number of pages10
JournalMucosal Immunology
Volume11
Issue number3
DOIs
Publication statusPublished - 2018 May 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Shibata, N., Kunisawa, J., Hosomi, K., Fujimoto, Y., Mizote, K., Kitayama, N., Shimoyama, A., Mimuro, H., Sato, S., Kishishita, N., Ishii, K. J., Fukase, K., & Kiyono, H. (2018). Lymphoid tissue-resident Alcaligenes LPS induces IgA production without excessive inflammatory responses via weak TLR4 agonist activity. Mucosal Immunology, 11(3), 693-702. https://doi.org/10.1038/mi.2017.103