Gut flora, Toll-like receptors and nuclear receptors: A tripartite communication that tunes innate immunity in large intestine

Annelie Lundin, Chek Mei Bok, Linda Aronsson, Britta Björkholm, Jan Åke Gustafsson, Sebastian Pott, Velmurugesan Arulampalam, Martin Hibberd, Joseph Rafter, Sven Pettersson

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

Separating the large intestine from gut flora is a robust layer of epithelial cells. This barrier is armed with an array of recognizing receptors that collectively set the host innate response. Here, we use nuclear receptors (NRs) and Toll-like receptors (TLRs), suggested to act as second messengers in the communication between microorganisms and epithelial cells, as probes to assess the impact of gut flora on innate immunity in germ-free (GF) mice. Using quantitative real-time polymerase chain reaction analyses, we show that 37/49 NRs are expressed in colonic cells of GF mice. Of these, 5 can be modulated by resident flora: LXRα, RORγ and CAR show reduced expression and Nur77 and GCNF display elevated expression in conventionally raised mice compared with GF. Moreover, increased expression levels of TLR-2 and TLR-5 are observed in specific pathogen-free (SPF) mice compared with GF mice, and CAR expression is connected to the TLR-2 signalling pathway. Infections of GF or SPF mice with Yersinia pseudotuberculosis, show that GF intestinal epithelial cells fail to respond, except for CAR, which is downregulated. In contrast, SPF epithelial cells show a downregulation of all the NRs except CAR, which appears to be unaffected. Our findings indicate that gut flora contributes to the development of an intact barrier function.

Original languageEnglish (US)
Pages (from-to)1093-1103
Number of pages11
JournalCellular Microbiology
Volume10
Issue number5
DOIs
StatePublished - May 2008

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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