Related Experiment Video
Updated: Jun 20, 2025
Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
CRIg+ macrophages deficiency enhanced inflammation damage in IBD due to gut extracellular vesicles containing
Shangshu Nie1, Zhongchao Zhang1, Yudong Ji2
1Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Gut microbiota-derived extracellular vesicles (mEVs) are reported to regulate inflammatory response by delivering bacterial products into host cells. The complement receptor of the immunoglobulin superfamily macrophages (CRIg+ Mφ) could clear invading bacteria and their derivatives. Here, we investigate the role of CRIg+ Mφ and the mechanism by which mEVs regulate intestinal inflammation. We found that it is exacerbated in IBD patients and colitis mice by mEVs' leakage from disturbed gut microbiota, enriching microbial DNA in the intestinal mucosa. CRIg+ Mφ significantly decrease in IBD patients, allowing the spread of mEVs into the mucosa. The microbial DNA within mEVs is the key trigger for inflammation and barrier function damage. The cGAS/STING pathway is crucial in mEVs-mediated inflammatory injury. Blocking cGAS/STING signaling effectively alleviates inflammation caused by mEVs leakage and CRIg+ Mφ deficiency. Microbial DNA-containing mEVs, along with CRIg+ Mφ deficiency, stimulate inflammation in IBD, with the cGAS/STING pathway playing a crucial role.
Insights
Microbial DNA in gut extracellular vesicles (mEVs) worsens intestinal inflammation in inflammatory bowel disease (IBD) when complement receptor of immunoglobulin superfamily macrophages (CRIg+ Mφ) are deficient. Blocking the cGAS/STING pathway reduces this inflammation.
Area of Science:
- Gastroenterology and Immunology
- Microbiome Research
- Cellular Signaling Pathways
Background:
- Gut microbiota-derived extracellular vesicles (mEVs) deliver bacterial products, influencing host inflammatory responses.
- Complement receptor of immunoglobulin superfamily macrophages (CRIg+ Mφ) are critical for clearing bacterial invaders.
- Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation.
Purpose of the Study:
- To investigate the role of CRIg+ Mφ in intestinal inflammation mediated by mEVs.
- To elucidate the mechanism by which mEVs regulate intestinal inflammation in IBD.
- To identify therapeutic targets for mEVs-induced inflammation.
Main Methods:
- Analysis of mEVs and CRIg+ Mφ in IBD patients and colitis mouse models.
- Investigation of microbial DNA within mEVs as an inflammatory trigger.
- Assessment of the cGAS/STING signaling pathway's involvement in mEVs-mediated inflammation.
- Evaluation of cGAS/STING pathway inhibition as a therapeutic strategy.
Main Results:
- mEVs leakage from disturbed gut microbiota exacerbates intestinal inflammation in IBD and colitis models.
- CRIg+ Mφ are significantly reduced in IBD patients, facilitating mEVs spread.
- Microbial DNA within mEVs triggers inflammation and damages the intestinal barrier via the cGAS/STING pathway.
- Blocking cGAS/STING signaling effectively alleviates inflammation caused by mEVs leakage and CRIg+ Mφ deficiency.
Conclusions:
- Microbial DNA-containing mEVs, coupled with CRIg+ Mφ deficiency, drive inflammation in IBD.
- The cGAS/STING pathway is a critical mediator of mEVs-induced inflammatory injury.
- Targeting the cGAS/STING pathway offers a potential therapeutic approach for IBD management.
Related Concept Videos
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:17Chronic Bowel Disorders: Introduction
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
01:17Irritable Bowel Syndrome I: Introduction
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF