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Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis.

ABSTRACT: Inflammasomes are involved in gut homeostasis and inflammatory pathologies, but the role of NLRP3 inflammasome in these processes is not well understood. Cryopyrin-associated periodic syndrome (CAPS) patients with NLRP3 mutations have autoinflammation in skin, joints, and eyes, but not in the intestine. Here we show that the intestines of CAPS model mice carrying an Nlrp3 R258W mutation maintain homeostasis in the gut. Additionally, such mice are strongly resistant to experimental colitis and colorectal cancer; this is mainly through a remodelled gut microbiota with enhanced anti-inflammatory capacity due to increased induction of regulatory T cells (Tregs). Mechanistically, NLRP3R258W functions exclusively in the lamina propria mononuclear phagocytes to directly enhance IL-1? but not IL-18 secretion. Increased IL-1? boosts local antimicrobial peptides to facilitate microbiota remodelling. Our data show that NLRP3R258W-induced remodelling of the gut microbiota, induces local Tregs to maintain homeostasis and compensate for otherwise-detrimental intestinal inflammation.

SUBMITTER: Yao X

PROVIDER: S-EPMC5711854 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis.

Yao Xiaomin X Zhang Chenhong C Xing Yue Y Xue Guang G Zhang Qianpeng Q Pan Fengwei F Wu Guojun G Hu Yingxin Y Guo Qiuhong Q Lu Ailing A Zhang Xiaoming X Zhou Rongbin R Tian Zhigang Z Zeng Benhua B Wei Hong H Strober Warren W Zhao Liping L Meng Guangxun G

Nature communications 20171201 1

Inflammasomes are involved in gut homeostasis and inflammatory pathologies, but the role of NLRP3 inflammasome in these processes is not well understood. Cryopyrin-associated periodic syndrome (CAPS) patients with NLRP3 mutations have autoinflammation in skin, joints, and eyes, but not in the intestine. Here we show that the intestines of CAPS model mice carrying an Nlrp3 <sup>R258W</sup> mutation maintain homeostasis in the gut. Additionally, such mice are strongly resistant to experimental col ...[more]

PMID: 29196621

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Project description:The gut microbiota is an integral part of the host and has a functional potential in host physiology. Numerous scientific efforts have opened new horizons in gut microbiota research and enhanced the understanding of host-microbe interactions in vertebrates. However, evidence on the association between the gut microbiota and immunity in invertebrates, especially in shrimp, which is an important aquatic animal, is limited. Herein, we conducted a comprehensive analysis based on 16S rRNA gene sequencing and liquid chromatography-coupled mass spectrometry (LC-MS) to investigate the correlation between them. Comparing the gut microbiota among the four different species of shrimp, we found huge variations and determined a core gut microbiota composed of 55 microbes. The environmental challenge of white spot syndrome virus (WSSV) infection led to changes in core microbial structures, but the alteration of core microbiota among different shrimp followed the same trend and showed immune-related function in the prediction of its metabolic potential. In metabolomic analysis, nine significantly upregulated metabolites found after viral infection indicated that they have antiviral potential. Moreover, we found a tight correlation between them and almost half of the core microbiota. These data demonstrate that these metabolites are responsible for maintaining the immune homeostasis of the host and prove the function of the gut microbiota and the related metabolome in antiviral immunity of shrimp. IMPORTANCE Abundant gut microorganisms constitute a complex microecosystem with the intestinal environment of the host, which plays a critical role in the adjustment of various physiological states of the organism. Sequencing and mass spectrometry data collected from intestinal samples of shrimp after virus infection helped to investigate the special function of the microecosystem and suggested that the gut microbiota has a functional potential in maintaining immune homeostasis of the host under environmental challenge.

Dataset Information

Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis.

Publications

Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis.

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