Publikationsdatenbank

Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven Colitis (2019)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Meiners, Jana

Palmieri, Vittoria

Klopfleisch, Robert (WE 12)

Ebel, Jana-Fabienne

Japtok, Lukasz

Schumacher, Fabian

Yusuf, Ayan Mohamud

Becker, Katrin A

Zöller, Julia

Hose, Matthias

Kleuser, Burkhard

Hermann, Dirk M

Kolesnick, Richard N

Buer, Jan

Hansen, Wiebke

Westendorf, Astrid M

Quelle

Frontiers in immunology

Bandzählung: 10

Seiten: Article 1386

ISSN: 1664-3224

Sprache

Englisch

Verweise

URL (Volltext): https://www.frontiersin.org/articles/10.3389/fimmu.2019.01386/full

DOI: 10.3389/fimmu.2019.01386

Pubmed: 31275322

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Inflammatory diseases of the gastrointestinal tract are emerging as a global problem with increased evidence and prevalence in numerous countries. A dysregulated sphingolipid metabolism occurs in patients with ulcerative colitis and is discussed to contribute to its pathogenesis. In the present study, we determined the impact of acid sphingomyelinase (Asm), which catalyzes the hydrolysis of sphingomyelin to ceramide, on the course of Citrobacter (C.) rodentium-driven colitis. C. rodentium is an enteric pathogen and induces colonic inflammation very similar to the pathology in patients with ulcerative colitis. We found that mice with Asm deficiency or Asm inhibition were strongly susceptible to C. rodentium infection. These mice showed increased levels of C. rodentium in the feces and were prone to bacterial spreading to the systemic organs. In addition, mice lacking Asm activity showed an uncontrolled inflammatory Th1 and Th17 response, which was accompanied by a stronger colonic pathology compared to infected wild type mice. These findings identified Asm as an essential regulator of mucosal immunity to the enteric pathogen C. rodentium.