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Antibiotic-induced dysbiosis is a key predisposing factor for Clostridium difficile infections (CDIs), which cause intestinal disease ranging from mild diarrhea to pseudomembranous colitis. Here, we examined the impact of a microbiota-derived metabolite, short-chain fatty acid acetate, on an acute mouse model of CDI. We found that administration of acetate is remarkably beneficial in ameliorating disease. Mechanistically, we show that acetate enhances innate immune responses by acting on both neutrophils and ILC3s through its cognate receptor free fatty acid receptor 2 (FFAR2). In neutrophils, acetate-FFAR2 signaling accelerates their recruitment to the inflammatory sites, facilitates inflammasome activation, and promotes the release of IL-1β; in ILC3s, acetate-FFAR2 augments expression of the IL-1 receptor, which boosts IL-22 secretion in response to IL-1β. We conclude that microbiota-derived acetate promotes host innate responses to C. difficile through coordinate action on neutrophils and ILC3s.
This article was published in the following journal.
Name: The Journal of experimental medicine
Group 3 innate lymphoid cells (ILC3) play key roles in protective immunity and mucosal barrier maintenance. Here we showed that vitamin D/vitamin D receptor (VDR) signaling regulates gut ILC3. VDR del...
Circadian clock proteins BMAL1 and REV-ERBα harmonize the development and function of ILC3 (see related articles by Teng and Wang ).
Fecal calprotectin (FC) rises significantly in intestinal inflammation accompanied by neutrophil activation - such as Clostridium difficile infection (CDI). The aim of the study was to evaluate the be...
Previously, we found that pathological immune responses enhance the mortality rate of Mycobacterium tuberculosis (Mtb)-infected mice with type 2 diabetes mellitus (T2DM). In the current study, we eval...
After having included the most improved patients by DBS among those implanted in Bordeaux Hospital University, and having defined the most active plots on tremor by its prospective grading...
The purpose of this study is to establish which of the following tests perform best in diagnosing clostridium difficile. PCR, Enzyme Immunoassays (EIA) and C. difficile cytotoxin assay (C...
The Clover trial is evaluating an investigational vaccine that may help to prevent Clostridium difficile infection. Participants in the study are adults 50 years of age and older, who are ...
The objective of this study to evaluate the seroprevalence of anti-bodies against C. difficile toxins A and B and the asymptomatic carriage of C. difficile in IBD patients according to the...
The protocol aims to address the basic mechanisms of Clostridium difficile pathogenesis by identifying how Clostridium difficile toxins inhibit eosinophils that otherwise would protect the...
The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cell-surface receptors on the neutrophil.
An enzyme that catalyzes the conversion of acetate esters and water to alcohols and acetate. EC 126.96.36.199.
Megestrol acetate is a progestogen with actions and uses similar to those of the progestogens in general. It also has anti-androgenic properties. It is given by mouth in the palliative treatment or as an adjunct to other therapy in endometrial carcinoma and in breast cancer. Megestrol acetate has been approved to treat anorexia and cachexia. (From Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)
A 6-methyl PROGESTERONE acetate with reported glucocorticoid activity and effect on ESTRUS.
An enzyme that catalyzes the formation of CoA derivatives from ATP, acetate, and CoA to form AMP, pyrophosphate, and acetyl CoA. It acts also on propionates and acrylates. EC 188.8.131.52.
Clostridium difficile (CDI)
A clostridium difficile infection (CDI) is a type of bacterial infection that can affect the digestive system. It most commonly affects people who are staying in hospital. The symptoms of CDI can range from mild to severe and include: diarrhoe...
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...