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Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation

The glycosphingolipid, α-galactosylceramide (αGalCer), when presented by CD1d on antigen-presenting cells, efficiently activates invariant natural killer T (iNKT) cells. Thereby, it modulates immune responses against tumors, microbial and viral infections, and autoimmune diseases. Recently, the prod...

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Hauptverfasser: Gerichten, Johanna von (VerfasserIn) , Marsching, Christian (VerfasserIn) , Engel, Robert (VerfasserIn) , Herzer, Silke (VerfasserIn) , Galy, Bruno (VerfasserIn) , Nordström, Viola (VerfasserIn) , Hopf, Carsten (VerfasserIn) , Gröne, Hermann-Josef (VerfasserIn) , Sandhoff, Roger (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: September 4, 2019
In: Journal of lipid research
Year: 2019, Jahrgang: 60, Heft: 11, Pages: 1892-1904
ISSN:1539-7262
DOI:10.1194/jlr.RA119000236
Online-Zugang:Verlag, Volltext: https://doi.org/10.1194/jlr.RA119000236
Verlag, Volltext: http://www.jlr.org/content/60/11/1892
Volltext
Verfasserangaben:Johanna von Gerichten, Dominic Lamprecht, Lukáš Opálka, Daphnée Soulard, Christian Marsching, Robert Pilz, Valentin Sencio, Silke Herzer, Bruno Galy, Viola Nordström, Carsten Hopf, Hermann-Josef Gröne, François Trottein, Roger Sandhoff
Beschreibung
Zusammenfassung:The glycosphingolipid, α-galactosylceramide (αGalCer), when presented by CD1d on antigen-presenting cells, efficiently activates invariant natural killer T (iNKT) cells. Thereby, it modulates immune responses against tumors, microbial and viral infections, and autoimmune diseases. Recently, the production of αGalCer by Bacteroidetes from the human gut microbiome was elucidated. Using hydrophilic interaction chromatography coupled to MS2, we screened murine intestinal tracts to identify and quantify αGalCers, and we investigated the αGalCer response to different dietary and physiologic conditions. In both the cecum and the colon of mice, we found 1-15 pmol of αGalCer per milligram of protein; in contrast, mice lacking microbiota (germ-free mice) and fed identical diet did not harbor αGalCer. The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis. Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro. Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection. Collectively, this study suggests that αGalCer is produced by commensals in the mouse intestine and reveals that stressful conditions causing dysbiosis alter its synthesis. The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
Beschreibung:Gesehen am 19.12.2019
Beschreibung:Online Resource
ISSN:1539-7262
DOI:10.1194/jlr.RA119000236

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