Gut flora, Toll-like receptors and nuclear receptors: a tripartite communication that tunes innate immunity in large intestine.
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: LXRalpha, RORgamma 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.
Lundin
Annelie
A
Department of Microbiology, Cell and Tumor Biology, Karolinska Institutet, Stockholm 171 77, Sweden.
Bok
Chek Mei
CM
Aronsson
Linda
L
Björkholm
Britta
B
Gustafsson
Jan-Ake
JA
Pott
Sebastian
S
Arulampalam
Velmurugesan
V
Hibberd
Martin
M
Rafter
Joseph
J
Pettersson
Sven
S
D000818:Animals; D003092:Colitis / Q000276:immunology; D004847:Epithelial Cells; D005856:Germ-Free Life; D007113:Immunity, Innate; D007420:Intestine, Large / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology*; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051198:Toll-Like Receptor 5 / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*; D015011:Yersinia pseudotuberculosis / Q000502:physiology
D018160:Receptors, Cytoplasmic and Nuclear; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors