Principal Investigator:

Prof. Dr. rer. nat. Astrid Westendorf
Institute of Medical Microbiology
University Hospital Essen
University of Duisburg-Essen

astrid.westendorf@uk-essen.de

Phone: +49 201 723 1826

Interleukin-33-mediated dysbiosis and
the consequences for enteric bacterial infection

A wide range of microbial pathogens is capable of entering the gastrointestinal tract, causing infectious diarrhea and colitis. The finely tuned balance between pro- and anti-inflammatory cytokines is necessary to eradicate the microbial threat and to avoid infection complications. Recently, we identified IL-33 as a critical negative regulator of the immune response to the enteric pathogen Citrobacter rodentium. Interestingly, first results demonstrate that treatment of mice with IL-33 modulates the microbial composition in the colon. Therefore, in the present project we want to dissect whether the IL-33-induced alterations of the gut microbiota modulate the immune system and contribute to the hosts’ susceptibility to Citrobacter rodentium infection. A better understanding of cytokine-mediated changes in the microbial composition and the modulation of host immune responses in the gut is important for the treatment of intestinal infectious diseases.  

Publications

Pastille E, Wasmer MH, Adamczyk A, Vu VP, Mager LF, Phuong NNT, Palmieri V, Simillion C, Hansen W, Kasper S, Schuler M, Muggli B, McCoy KD, Buer J, Zlobec I, Westendorf AM, Krebs P. The IL-33/ST2 pathway shapes the regulatory T cell phenotype to promote intestinal cancer. Mucosal Immunol. 2019 Jul; 12(4):990-1003. doi: 10.1038/s41385-019-0176-y.

Meiners J, Palmieri V, Klopfleisch R, Ebel JF, Japtok L, Schumacher F, Yusuf AM, Becker KA, Zöller J, Hose M, Kleuser B, Hermann DM, Kolesnick RN, Buer J, Hansen W, Westendorf AM. Intestinal acid sphingomyelinase protects from severe pathogen-driven colitis. Front Immunol. 2019 Jun 19; 10:1386. doi: 10.3389/fimmu.2019.01386.

Knuschke T, Rotan O, Bayer W, Sokolova V, Hansen W, Sparwasser T, Dittmer U, Epple M, Buer J, Westendorf AM. Combination of nanoparticle-based therapeutic vaccination and transient ablation of regulatory T cells enhances anti-viral immunity during chronic retroviral infection. Retrovirology. 2016 Apr 14;13(1):24. doi: 10.1186/s12977-016-0258-9.

Seiffart V, Zoeller J, Klopfleisch R, Wadwa M, Hansen W, Buer J, Riedel C, Westendorf AM. IL10-deficiency in CD4 T cells exacerbates the IFNγ and IL17 response during bacteria induced Colitis. Cell Physiol Biochem. 2015 Jul 1;36(4):1259-1273.

Abel S, Luckheide N, Westendorf AM, Geffers R, Roers A, Muller W, Sparwasser T, Matuschewski K, Buer J, Hansen W. Strong Impact of CD4+Foxp3+ Regulatory T Cells and Limited Effect of T Cell-Derived IL-10 on Pathogen Clearance during Plasmodium yoelii Infection. J Immunol 2012;188(11):5467-77.

Fleissner D, Frede A, Knott M, Knuschke T, Geffers R, Hansen W, Dobos G, Langhorst J, Buer J, Westendorf AM. Generation and function of immunosuppressive human and murine CD8+ T cells by transforming growth factor-beta and retinoic acid. Immunology 2011;134:82-92.

Schenk U, Frascoli M, Proietti M, Geffers R, Traggiai E, Buer J, Ricordi C, Westendorf AM, Grassi F. ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. Sci Signal 2011;4(162):ra12.

Westendorf AM, Fleissner D, Groebe L, Jung S, Gruber AD, Hansen W, Buer J. CD4+Foxp3+ regulatory T cell expansion induced by antigen-driven interaction with intestinal epithelial cells independent of local dendritic cells. Gut 2009;58:211-9.

Hansen W, Westendorf AM, Reinwald S, Bruder D, Deppenmeier S, Groebe L, Probst-Kepper M, Gruber AD, Geffers R, Buer J. Chronic antigen stimulation in vivo induces a distinct population of antigen-specific Foxp3 CD25 regulatory T cells. J Immunol 2007;179:8059-68.

Westendorf AM, Fleissner D, Deppenmeier S, Gruber AD, Bruder D, Hansen W, Liblau R, Buer J. Autoimmune-mediated intestinal inflammation-impact and regulation of antigen-specific CD8+ T cells. Gastroenterology 2006;131:510-24.

Westendorf AM, Templin M, Geffers R, Deppenmeier S, Gruber AD, Probst-Kepper M, Hansen W, Liblau RS, Gunzer F, Bruder D, Buer J. CD4+ T cell mediated intestinal immunity: chronic inflammation versus immune regulation. Gut 2005;54:60-9.