Endotoxicity of Lipopolysaccharide as a Determinant of T-Cell−Mediated Colitis Induction in Mice

Gronbach, Kerstin; Flade, Isabell; Holst, Otto; Lindner, Buko; Ruscheweyh, Hans Joachim; Wittmann, Alexandra; Menz, Sarah; Schwiertz, Andreas; Adam, Patrick; Stecher, Bärbel; Josenhans, Christine; Suerbaum, Sebastian; Gruber, Achim D.; Kulik, Andreas; Huson, Daniel H.; Autenrieth, Ingo B.; Frick, Julia-Stefanie

doi:10.1053/j.gastro.2013.11.033

Cited by 71 publications

(64 citation statements)

References 52 publications

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“…Furthermore, a new study showed that there is a greater abundance of Escherichia-Shigella (a Proteobacteria) in the inflamed mucosae than in non-inflamed mucosae in UC patients (Baumgart et al, 2007;Xu et al, 2018). Moreover, Escherichia-Shigella is a Gram-negative bacterium that invades the human colonic epithelium and induces inflammatory responses owing to the presence of LPS in its outer membrane (Gronbach et al, 2014;Stephens and von der Weid, 2019). In our study, DSS treatment also led to an increase in the abundance of Escherichia-Shigella; however, this increase was attenuated with obacunone treatment.…”

Section: Discussionmentioning

confidence: 99%

Obacunone Protects Against Ulcerative Colitis in Mice by Modulating Gut Microbiota, Attenuating TLR4/NF-κB Signaling Cascades, and Improving Disrupted Epithelial Barriers

Yue

et al. 2020

Front. Microbiol.

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Section: Discussionmentioning

confidence: 99%

Obacunone Protects Against Ulcerative Colitis in Mice by Modulating Gut Microbiota, Attenuating TLR4/NF-κB Signaling Cascades, and Improving Disrupted Epithelial Barriers

Yue

et al. 2020

Front. Microbiol.

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“…Ϫ/Ϫ mouse model of colitis (24). It was demonstrated that LPS with higher levels of TLR4 activity was a key determinant of whether mice develop colitis in the adaptive transfer model.…”

Section: Discussionmentioning

confidence: 99%

“…This change in microbial community composition significantly alters the amount and type of LPS to which intestinal tissue is exposed. In fact, it was recently demonstrated in a mouse model system that Rag1 Ϫ/Ϫ mice harboring a high proportion of isolates of the family Enterobacteriaceae developed colitis (24). However, little is known concerning how the host may regulate LPS exposure to intestinal tissue in order to accomplish intestinal homeostasis and how LPS exposure is detrimental and associated with destructive inflammatory disease.…”

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confidence: 99%

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

Coats

Hashim

Paramonov

et al. 2016

Appl Environ Microbiol

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Intestinal homeostasis mechanisms must protect the host intestinal tissue from endogenous lipopolysaccharides (LPSs) produced by the intestinal microbiota. In this report, we demonstrate that murine intestinal fecal lipids effectively block Toll-like receptor 4 (TLR4) responses to naturally occurring Bacteroidetes sp. LPS. Cardiolipin (CL) represents a significant proportion of the total intestinal and fecal lipids and, furthermore, potently antagonizes TLR4 activation by reducing LPS binding at the lipopolysaccharide binding protein (LBP), CD14, and MD-2 steps of the TLR4 signaling pathway. It is further demonstrated that intestinal lipids and CL are less effective at neutralizing more potent Enterobacteriaceae-type LPS, which is enriched in feces obtained from mice with dextran sodium sulfate (DSS)-treated inflammatory bowel disease. The selective inhibition of naturally occurring LPS structures by intestinal lipids may represent a novel homeostasis mechanism that blocks LPS activation in response to symbiotic but not dysbiotic microbial communities. IMPORTANCEThe guts of animals harbor a variety of Gram-negative bacteria associated with both states of intestinal health and states of disease. Environmental factors, such as dietary habits, can drive the microbial composition of the host animal's intestinal bacterial community toward a more pathogenic state. Both beneficial and harmful Gram-negative bacteria are capable of eliciting potentially damaging inflammatory responses from the host intestinal tissues via a lipopolysaccharide (LPS)-dependent pathway. Physical mucosal barriers and antibodies produced by the intestinal immune system protect against the undesired inflammatory effects of LPS, although it is unknown why some bacteria are more effective at overcoming the protective barriers than others. This report describes the discovery of a lipid-type protective barrier in the intestine that reduces the deleterious effects of LPSs from beneficial bacteria but is less effective in dampening the inflammatory effects of LPSs from harmful bacteria, providing a novel mechanistic insight into inflammatory intestinal disorders.T he intestinal tract is constantly exposed to the potentially harmful effects of lipopolysaccharide (LPS), commonly referred to as endotoxin. Both internal sources, such as the intestinal microbiome, and external sources, such as food, provide a constant potential for endotoxin-mediated local or systemic injury. Several different innate and adaptive protective mechanisms present in the intestine facilitate a homeostatic relationship with the resident commensal microbiota and buffer food intake such that LPS does not impair normal intestinal tissue functions (1-5).Studies have shown that a major mechanism by which the intestine limits exposure to the potentially harmful effects of LPS is by preventing intestinal LPS-epithelial cell interactions through a physiochemical barrier consisting of a family of glycoproteins referred to as mucins. Mucins provide an effective barricade restrict...

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“…Whether perturbation of the microbiota is a cause or consequence of intestinal inflammation remains controversial. On one hand, microbiota directly regulate intestinal inflammation in several chemically-induced 18-20 , T cell transfer-induced 21 , and genetic mouse models 22,23 of colitis. In some instances, discreet species of naturally occurring enteric bacteria – termed pathobionts – have been identified that overgrow their niche upon exposure to high fat diet 24 or broad spectrum antibiotics 25 and promote IBD-like intestinal pathology.…”

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confidence: 99%

Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases

Chen

Sundrud

2016

Inflammatory Bowel Diseases

130

104

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Pathogenesis of the inflammatory bowel diseases (IBDs) ulcerative colitis (UC) and Crohn’s disease (CD) involve pro-inflammatory changes within the microbiota, chronic immune-mediated inflammatory responses, and epithelial dysfunction. Converging data from genome-wide association studies (GWAS), mouse models of IBD, and clinical trials indicate that cytokines are key effectors of both normal homeostasis and chronic inflammation in the gut. Yet still many questions remain concerning the role of specific cytokines in different IBDs, within distinct regions of the gut, and with regard cellular mechanisms of action. Here we review current and emerging concepts concerning the role of cytokines in IBD, with a focus on immune regulation, T cell subsets, and potential clinical applications.

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Endotoxicity of Lipopolysaccharide as a Determinant of T-Cell−Mediated Colitis Induction in Mice

Abstract: The endotoxicity of LPS produced by the intestinal microbiota is a determinant of whether mice develop colitis after transfer of CD4(+)CD62L(+) T cells. This finding might aid the design of novel biologics or probiotics to treat inflammatory bowel disease.

Cited by 71 publications

References 52 publications

Obacunone Protects Against Ulcerative Colitis in Mice by Modulating Gut Microbiota, Attenuating TLR4/NF-κB Signaling Cascades, and Improving Disrupted Epithelial Barriers

Obacunone Protects Against Ulcerative Colitis in Mice by Modulating Gut Microbiota, Attenuating TLR4/NF-κB Signaling Cascades, and Improving Disrupted Epithelial Barriers

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases

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