AUTHOR=Meiners Jana , Palmieri Vittoria , Klopfleisch Robert , 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. 

TITLE=Intestinal Acid Sphingomyelinase Protects From Severe Pathogen-Driven Colitis

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01386

DOI=10.3389/fimmu.2019.01386

ISSN=1664-3224

ABSTRACT=<p>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 <italic>Citrobacter (C.) rodentium</italic>-driven colitis. <italic>C. rodentium</italic> 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 <italic>C. rodentium</italic> infection. These mice showed increased levels of <italic>C. rodentium</italic> in the feces and were prone to bacterial spreading to the systemic organs. In addition, mice lacking Asm activity showed an uncontrolled inflammatory T<sub>h</sub>1 and T<sub>h</sub>17 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 <italic>C. rodentium</italic>.</p>