Transitions in oral and intestinal microflora composition and innate immune receptor-dependent stimulation during mouse development

Mizuho Hasegawa, Toshifumi Osaka, Kazuki Tawaratsumida, Takashi Yamazaki, Hiroyuki Tada, Grace Y. Chen, Satoshi Tsuneda, Gabriel Núñez, Naohiro Inohara

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Commensal bacteria possess immunostimulatory activities that can modulate host responses to affect development and homeostasis in the intestine. However, how different populations of resident bacteria stimulate the immune system remains largely unknown. We characterized here the ability of intestinal and oral microflora to stimulate individual pattern recognition receptors (PRRs) in bone marrow-derived macrophages and mesothelial cells. The intestinal but not oral microflora elicited age- and cell type-specific immunostimulation. The immunostimulatory activity of the intestinal microflora varied among individual mice but was largely mediated via Toll-like receptor 4 (TLR4) during breast-feeding, whereas it became TLR4 independent after weaning. This transition was associated with a change from a microflora rich in TLR4-stimulatory proteobacteria to one dominated by Bacteroidales and/or Clostridiales that poorly stimulate TLR4. The major stimulatory activity of the intestinal microflora was still intact in NOD1-, NOD2-, TLR2-, TLR4-, TLR5-, TLR9-, TLR11-, ASC-, or RICK-deficient cells but still relied on the adaptor MyD88. These studies demonstrate a transition in the intestinal microflora accompanied by a dynamic change of its ability to stimulate different PRRs which control intestinalE homeostasis.

Original languageEnglish
Pages (from-to)639-650
Number of pages12
JournalInfection and Immunity
Volume78
Issue number2
DOIs
Publication statusPublished - 2010 Feb 1

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Hasegawa, M., Osaka, T., Tawaratsumida, K., Yamazaki, T., Tada, H., Chen, G. Y., Tsuneda, S., Núñez, G., & Inohara, N. (2010). Transitions in oral and intestinal microflora composition and innate immune receptor-dependent stimulation during mouse development. Infection and Immunity, 78(2), 639-650. https://doi.org/10.1128/IAI.01043-09