Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome

Bauer, Christian; Duewell, Peter; Mayer, Christine; Lehr, Hans A.; Fitzgerald, Katherine A.; Dauer, Marc; Tschopp, Jürg; Endres, Stefan; Latz, Eicke; Schnurr, Max

doi:10.1136/gut.2009.197822

Cited by 762 publications

(507 citation statements)

References 39 publications

(47 reference statements)

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“…Combined, these data suggest that in mice lacking the pan-inflammasome adaptor protein ASC, there is an outgrowth of bacteria that could be implicated in a dysbiotic microbiome. This interpretation would be consistent with the previously reported increased sensitivity of these mice to models of experimental colitis and colitis-associated cancer [18, 29]. …”

Section: Resultssupporting

confidence: 82%

“…Mice lacking the pan-inflammasome adaptor protein ASC are highly sensitive to experimental colitis and demonstrate significantly increased inflammation-driven colon tumorigenesis [9-11, 15, 29]. Surprisingly, there are few comprehensive studies evaluating the microbiome composition in the Asc –/– mice under naïve conditions and, of those that have been conducted, there is currently conflicting data regarding the role of ASC in shaping the commensal gut microbiota composition [18, 21].…”

Section: Resultsmentioning

confidence: 99%

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Maternal Influence and Murine Housing Confound Impact of NLRP1 Inflammasome on Microbiome Composition

Ringel‐Scaia

Qin²,

Thomas

et al. 2019

J Innate Immun

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The NLRP1 inflammasome attenuates inflammatory bowel disease (IBD) progression and colitis-associated tumorigenesis. A possible mechanism postulates that the lack of the NLRP1 inflammasome creates permissive niches in the gut for pathogenic bacteria to flourish, causing dysbiosis and increased IBD susceptibility. To evaluate this hypothesis, we characterized the gut microbiome of wild-type, Nlrp1b–/–, and Asc–/– mice under naïve conditions by sequencing the V3 region of the 16s rRNA gene. For both genetically modified mouse lines, the microbiome composition reflected overrepresentation of bacteria associated with dysbiosis relative to wild-type animals. Measurement of short- and medium-chain fatty acids by mass spectrometry further revealed significant differences between genotypes. However, prior to concluding that the NLRP1 inflammasome plays a role in regulating the composition of the microbiome, we evaluated two additional strategies for cohousing wild-type and Nlrp1b–/– mice: breeding homozygous parents and cohousing at weaning, and breeding from heterozygous parents and cohousing littermates. We found that maternal influence was the greater predictor of microbiome composition rather than genotype. With the rise in microbiome research across disciplines, our study should be viewed as a cautionary example that illustrates the importance of careful breeding and housing strategies when evaluating host-microbiome interactions.

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Maternal Influence and Murine Housing Confound Impact of NLRP1 Inflammasome on Microbiome Composition

Ringel‐Scaia

Qin²,

Thomas

et al. 2019

J Innate Immun

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“…Several lines of data from gene-deleted mouse models showed that the NLRP3 inflammasome protects against experimental colitis 36 and colitis-associated tumorigenesis, 37 whereas other groups demonstrated that NLRP3-PYCARD-CASP1-mediated maturation of IL1B is essential for DSS-induced experimental colitis and nlrp3 −/− mice develop a less severe colitis than wildtype mice. [38][39][40][41] Bauer et al pointed out that these contradictions might result from the different composition of the intestinal microflora. 41 Unlike the controversies resulting from genedeleted mouse models, IL18 neutralization, 42,43 or chemical CASP1 inhibitor 44,45 treatment effectively reduce severity in murine colitis.…”

Section: Discussionmentioning

confidence: 99%

Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer

et al. 2014

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“…In this scenario, various derivatives of dextran have shown to have immunological properties. The sulphatederivatized form of dextran sulphate was shown to have anti-inflammatory properties in vivo and it was used in the induction of inflammatory colitis in mice [13]. Another derivative, diethylaminoethyl dextran (DEAED), is polycationic in nature and has been used as a vaccine adjuvant.…”

Section: Natural Polymersmentioning

confidence: 99%

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

Shakya

Nandakumar

2013

J. R. Soc. Interface.

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Polymers as an adjuvant are capable of enhancing the vaccine potential against various infectious diseases and also are being used to study the actual autoimmune responses using self-antigen(s) without involving any major immune deviation. Several natural polysaccharides and their derivatives originating from microbes and plants have been tested for their adjuvant potential. Similarly, numerous synthetic polymers including polyelectrolytes, polyesters, polyanhydrides, non-ionic block copolymers and external stimuli responsive polymers have demonstrated adjuvant capacity using different antigens. Adjuvant potential of these polymers mainly depends on their solubility, molecular weight, degree of branching and the conformation of polymeric backbone. These polymers have the ability not only to activate humoral but also cellular immune responses in the host. The depot effect, which involves slow release of antigen over a long duration of time, using different forms (particulate, solution and gel) of polymers, and enhances the co-stimulatory signals for optimal immune activation, is the underlying principle of their adjuvant properties. Possibly, polymers may also interact and activate various toll-like receptors and inflammasomes, thus involving several innate immune system players in the ensuing immune response. Biocompatibility, biodegradability, easy production and purification, and non-toxic properties of most of the polymers make them attractive candidates for substituting conventional adjuvants that have undesirable effects in the host.

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Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome

Cited by 762 publications

References 39 publications

Maternal Influence and Murine Housing Confound Impact of NLRP1 Inflammasome on Microbiome Composition

Maternal Influence and Murine Housing Confound Impact of NLRP1 Inflammasome on Microbiome Composition

Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

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