Projects Mucosal Infection Immunology

Immunometabolism in intestinal infections

Targeting the intracellular metabolism of immune cells is a promising novel strategy for immunomodulation. Our previous work suggested that intracellular de novo fatty acid synthesis represents an important metabolic checkpoint for the reciprocal differentiation of Th17 versus regulatory T cells. One focus of our work is to understand the impact of central metabolic processes on intestinal immune responses under in vivo conditions. We use established as well as newly generated genetic mouse models that allow for the deletion of the key metabolic enzymes in specific immune- and non-immune cells such as T-cells, ILCs and intestinal epithelial cells. We also assess the potential of pharmacologic modulation of metabolic pathways and translate these findings into the human system.

Publications

Immune cell function in intestinal infections

It has been a long-standing focus of our research group to analyze the immune response in gut inflammation and infection with gut-specific bacterial pathogens. In particular, we study the role of dendritic cells for the induction of protective innate lymphoid cell (ILC)- and T cell-mediated immune responses in the intestine. Another focus is on the identification and functional characterization of epigenetic signature genes in ILC lineages, which will be an important step for the discovery of key pathways and molecular mechanisms in ILC differentiation and function in intestinal infection and inflammation. C. difficile is one of the most important causes of healthcare acquired infectious diarrhea. Using a newly established murine infection model, we aim to identify and to characterize processes associated with C. difficile infection, including the role of specific immune cell subpopulations or the impact of specific environmental and host-derived factors on the integrity of the intestinal barrier during acute/relapsing infection.

Publications

Immunometabolism in intestinal infections

Raud B, Roy DG, Divakaruni AS, Tarasenko TN, Franke R, Ma EH, Samborska B, Hsieh WY, Wong AH, Stüve P, Arnold-Schrauf C, Guderian M, Lochner M, Rampertaap S, Romito K, Monsale J, Brönstrup M, Bensinger SJ, Murphy AN, McGuire PJ, Jones RG, Sparwasser T, Berod L (2018) Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation. Cell Metab. 2018 Jun 19

Almeida, L.*, Lochner, M.*, Berod, L*. and T. Sparwasser. 2016. Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol 28(5): 514 - 524.

Lochner, M., L. Berod, and T. Sparwasser. 2015. Fatty acid metabolism in the regulation of T cell function. Trends Immunol 36:81-91.

Castro, C.N., J. Freitag, L. Berod, M. Lochner, and T. Sparwasser. 2015. Microbe-associated immunomodulatory metabolites: Influence on T cell fate and function. Mol Immunol 68:575-584.

Berod, L., C. Friedrich, A. Nandan, J. Freitag, S. Hagemann, K. Harmrolfs, A. Sandouk, C. Hesse, C.N. Castro, H. Bahre, S.K. Tschirner, N. Gorinski, M. Gohmert, C.T. Mayer, J. Huehn, E. Ponimaskin, W.R. Abraham, R. Muller, M. Lochner*, and T. Sparwasser*. 2014. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nature Medicine 20(11): 1327-33

Funding: DFG (KFO 250, LO 1415/7-1)

Immune cell function in intestinal infections

Friedrich, C., Mamareli. P., Thiemann, S., Kruse, F., Wang, Z., Holzmann, B., Strowig, T., Sparwasser, T. and M. Lochner. 2017. MyD88 signaling in dendritic cells and the intestinal epithelium controls immunity against intestinal infection with C. rodentium. PLOS Pathogens 13(5): 1-26.

Buettner, M., and M. Lochner, Development and function of secondary and tertiary lymphoid organs in the small intestine and the colon. 2016. Front Immunol 7 342.

Yang, B.H., S. Hagemann, P. Mamareli, U. Lauer, U. Hoffmann, M. Beckstette, L. Foehse, I. Prinz, J. Pezoldt, S. Suerbaum, T. Sparwasser, A. Hamann, S. Floess, J. Huehn, and M. Lochner, Foxp3+ T cells expressing RORgammat represent a stable regulatory T cell effector lineage with enhanced suppressive capacity during intestinal inflammation. 2016 Mucosal Immunology 9(2):444-57.

Yang, B.H., S. Floess, S. Hagemann, I.V. Deyneko, L. Groebe, J. Pezoldt, T. Sparwasser, M. Lochner, and J. Huehn. 2015. Development of a unique epigenetic signature during in vivo Th17 differentiation. Nucleic Acids Res 43:1537-1548.

Wang, Z., C. Friedrich, S.C. Hagemann, W.H. Korte, N. Goharani, S. Cording, G. Eberl, T. Sparwasser, and M. Lochner, Regulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium. 2014. Mucosal Immunology 7(6): 1290-301.

Lochner, M., C. Ohnmacht, L. Presley, P. Bruhns, M. Si-Tahar, S. Sawa, and G. Eberl, Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of ROR{gamma}t and LTi cells. 2011. J Exp Med 208:125-34.

Funding: DFG (KFO 250, LO 1415/7-1, LO1415/8-1), Volkswagen Foundation (CDIFF)