Regulation of toll-like receptors in intestinal epithelial cells by stress and Toxoplasma gondii infection.
Intestinal epithelial cells (IECs) form a barrier between invading microorganisms and the underlying host tissues. IECs express toll-like receptors (TLRs) that recognize specific molecular signatures on microbes, which activate intracellular signalling pathways leading to production of proinflammatory cytokines and chemokines. Stress hormones play an important role in modulation of proinflammatory cytokines and down-regulation of immune responses. Here we demonstrated that expression levels of TLR-2, TLR-4, TLR-9 and TLR-11 were significantly increased in mouse IECs following infection with Toxoplasma gondii on day 8 postinfection. In contrast, expression of TLRs was significantly decreased in infected mice subjected to cold water stress (CWS + INF). Expression of TLR-9 and TLR-11 in the mouse MODE-K cell line was significantly increased after infection. Expression of TLR-9 and TLR-11 in cells exposed to norepinephrine (NE) and parasites was significantly decreased when compared to cells exposed to parasites only. A significant increase was observed in SIGIRR, a negative regulator of TLRs in the CWS + INF group when compared to the INF group. Stress components were able to decrease expression levels of TLRs in IECs, decrease parasite load, and increase expression of a negative regulator thereby ameliorating intestinal inflammatory responses commonly observed during per oral T. gondii infection in C57BL/6 mice.
Gopal
R
R
Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011, USA.
Birdsell
D
D
Monroy
F P
FP
D000818:Animals; D002460:Cell Line; D003080:Cold Temperature; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000276:immunology*; D013566:Sympathomimetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*
D013566:Sympathomimetics; D051193:Toll-Like Receptors; D009638:Norepinephrine