Escherichia coli Strain Nissle 1917 Ameliorates Experimental Colitis via Toll-Like Receptor 2- and Toll-Like Receptor 4-Dependent Pathways

Abstract

Toll-like receptors (TLRs) are key components of the innate immune system that trigger antimicrobial host defense responses. The aim of the present study was to analyze the effects of probiotic Escherichia coli Nissle strain 1917 in experimental colitis induced in TLR-2 and TLR-4 knockout mice. Colitis was induced in wild-type (wt), TLR-2 knockout, and TLR-4 knockout mice via administration of 5% dextran sodium sulfate (DSS). Mice were treated with either 0.9% NaCl or 10 7 E. coli Nissle 1917 twice daily, followed by the determination of disease activity, mucosal damage, and cytokine secretion. wt and TLR-2 knockout mice exposed to DSS developed acute colitis, whereas TLR-4 knockout mice developed significantly less inflammation. In wt mice, but not TLR-2 or TLR-4 knockout mice, E. coli Nissle 1917 ameliorated colitis and decreased proinflammatory cytokine secretion. In TLR-2 knockout mice a selective reduction of gamma interferon secretion was observed after E. coli Nissle 1917 treatment. In TLR-4 knockout mice, cytokine secretion was almost undetectable and not modulated by E. coli Nissle 1917, indicating that TLR-4 knockout mice do not develop colitis similar to the wt mice. Coculture of E. coli Nissle 1917 and human T cells increased TLR-2 and TLR-4 protein expression in T cells and increased NF-B activity via TLR-2 and TLR-4. In conclusion, our data provide evidence that E. coli Nissle 1917 ameliorates experimental induced colitis in mice via TLR-2-and TLR-4-dependent pathways.

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

“…Several mechanisms have been raised to be responsible for the potential beneficial effects of probiotics, such as production of bactericidal substances, competition with pathogens and toxins for adherence to the intestinal epithelium, enhancement of the innate immunity, modulation of pathogen-induced inflammation via TLRregulated signaling pathways and stimulation of intestinal epithelial cell survival and barrier functions (see review [332]). Results from experimental models of colitis suggest that TLR2, TLR4 and TLR9 are necessary for some probiotics to exert their anti-inflammatory effects in vivo [333]. However, in the light of literature probiotics show variable evidence for their efficacy [334,335].…”

Current and Novel Treatments for Ulcerative Colitis

“…Additionally, infiltration of the colon with leukocytes was ameliorated in E.coli Nissle 1917 inoculated mice (191). Furthermore, Grabig et al (193) demonstrated that E. coli Nissle 1917 treatment in a wildtype DSS-induced colitis mouse model significantly reduced pro-inflammatory cytokine expression, myeloperoxidase (found in the intracellular granules of neutrophils) activity and disease activity. The inability of E. coli Nissle 1917 to exert its beneficial effect in the absence of toll-like receptor (TLR)-2 and TLR4 signaling using TLR2 and TLR4 knockout mice indicates that the amelioration of experimentallyindiced colitis in mice was elicited via TLR2-and TLR4-dependent pathways (193).…”

“…Furthermore, Grabig et al (193) demonstrated that E. coli Nissle 1917 treatment in a wildtype DSS-induced colitis mouse model significantly reduced pro-inflammatory cytokine expression, myeloperoxidase (found in the intracellular granules of neutrophils) activity and disease activity. The inability of E. coli Nissle 1917 to exert its beneficial effect in the absence of toll-like receptor (TLR)-2 and TLR4 signaling using TLR2 and TLR4 knockout mice indicates that the amelioration of experimentallyindiced colitis in mice was elicited via TLR2-and TLR4-dependent pathways (193). This finding highlights the fact that E. coli Nissle 1917 may improve the ability of TLRs, which are key components of the innate immune system that trigger antimicrobial host defence responses, to recognise microbial pathogens, improving the host immune response.…”

Role of Toll-like receptors in the development of immunotolerance mediated by probiotics

“…Grabig et al studied TLR2 and TLR4 knockout mice and demonstrated that E. coli Nissle 1917 fails to improve colitis or modulate cytokine production in comparison with wild-type mice (54) . Likewise, Hoarau et al reported that a fermentation product from Bifidobacterium breve C50 could induce maturation, high IL-10 production and prolonged survival of DCs via the TLR2 pathway (55) .…”