CX3CR1 is a gatekeeper for intestinal barrier integrity in mice: Limiting steatohepatitis by maintaining intestinal homeostasis

Autor: John Penders, Kai Markus Schneider, Wei Hu, Andreas Ludwig, Frank Tacke, Lijun Liao, Daniela Dreymueller, Nikolaus Gassler, Gernot Sellge, Veerle Bieghs, Oliver Pabst, Felix Heymann, Christian Trautwein, M. Frissen, Eicke Latz
Přispěvatelé: Moleculaire Genetica, Med Microbiol, Infect Dis & Infect Prev, RS: NUTRIM - R2 - Gut-liver homeostasis, RS: CAPHRI - R4 - Health Inequities and Societal Participation
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Male
Blood Glucose
Macrophage polarization
CX3C Chemokine Receptor 1
Inflammation
pharmacology [Anti-Bacterial Agents]
metabolism [Intestinal Mucosa]
microbiology [Intestines]
Biology
Gut flora
Liver disease
Mice
Nonalcoholic fatty liver disease
medicine
Animals
Homeostasis
ddc:610
MACROPHAGES
FATTY LIVER-DISEASE
INSULIN-RESISTANCE
Hepatology
immunology [Non-alcoholic Fatty Liver Disease]
NONALCOHOLIC STEATOHEPATITIS
Microbiota
GUT MICROBIOTA
NLRP3 INFLAMMASOME ACTIVATION
physiology [Macrophages]
AKKERMANSIA-MUCINIPHILA
medicine.disease
biology.organism_classification
metabolism [Non-alcoholic Fatty Liver Disease]
Immunity
Innate

Anti-Bacterial Agents
Mice
Inbred C57BL

Bacterial Translocation
physiology [Receptors
Chemokine]

OBESITY
Immunology
METABOLIC DISEASE
Increased inflammatory response
Receptors
Chemokine

Steatohepatitis
Metabolic syndrome
medicine.symptom
Cx3cr1 protein
mouse

analysis [Blood Glucose]
FRACTALKINE/CX3CR1 SYSTEM
Zdroj: Hepatology, 62(5), 1405-1416. Wiley
Hepatology 62(5), 1405-1416 (2015). doi:10.1002/hep.27982
ISSN: 0270-9139
DOI: 10.1002/hep.27982
Popis: Nonalcoholic fatty liver disease is seen as the hepatic manifestation of the metabolic syndrome and represents the most common liver disease in Western societies. The G protein-coupled chemokine receptor CX3CR1 plays a central role in several metabolic syndrome-related disease manifestations and is involved in maintaining intestinal homeostasis. Because diet-induced intestinal dysbiosis is a driver for nonalcoholic fatty liver disease, we hypothesized that CX3CR1 may influence the development of steatohepatitis. In two independent models of diet-induced steatohepatitis (high-fat diet and methionine/choline-deficient diet), CX3CR1 protected mice from excessive hepatic steatosis and inflammation, as well as systemic glucose intolerance. Lack of Cx3cr1 expression was associated with significantly altered intestinal microbiota composition, which was linked to an impaired intestinal barrier. Concomitantly, endotoxin levels in portal serum and inflammatory macrophages in liver were increased in Cx3cr1(-/-) mice, indicating an increased inflammatory response. Depletion of intestinal microbiota by administration of broad-spectrum antibiotics suppressed the number of infiltrating macrophages and promoted macrophage polarization in liver. Consequently, antibiotic-treated mice demonstrated a marked improvement of steatohepatitis. Conclusion: Microbiota-mediated activation of the innate immune responses through CX3CR1 is crucial for controlling steatohepatitis progression, which recognizes CX3CR1 as an essential gatekeeper in this scenario. (Hepatology 2015;62:1405-1416)
Databáze: OpenAIRE