TY  - JOUR
A1  - Meiners, Jana
A1  - Palmieri, Vittoria
A1  - Klopfleisch, Robert
A1  - Ebel, Jana-Fabienne
A1  - Japtok, Lukasz
A1  - Schumacher, Fabian
A1  - Yusuf, Ayan Mohamud
A1  - Becker, Katrin Anne
A1  - Zöller, Julia
A1  - Hose, Matthias
A1  - Kleuser, Burkhard
A1  - Hermann, Dirk Matthias
A1  - Kolesnick, Richard N.
A1  - Buer, Jan
A1  - Hansen, Wiebke
A1  - Westendorf, Astrid M.
T1  - Intestinal acid sphingomyelinase protects from severe Pathogen-Driven Colitis
JF  - Frontiers in immunology
N2  - 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 T(h)1 and T(h)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 C. rodentium.
KW  - Citrobacter rodentium
KW  - colitis
KW  - acid sphingomyelinase
KW  - amitriptyline
KW  - T(h)1
KW  - T(h)17
Y1  - 2019
U6  - https://doi.org/10.3389/fimmu.2019.01386
SN  - 1664-3224
VL  - 10
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  -