Projects Infection Immunology

Projects Infection Immunology

Therapeutic use of microbial immunomodulators

The number of potential gut bacterial metabolites is presently unknown, comprising molecules of dietary, host and microbial origin entangled in a complex, fascinating interplay between host, bacteria and the immune system. Making use of a unique library of bacterial metabolites, we, together with our partners at HZI, HIPS and MHH, have already identified promising candidates which directly and indirectly impact on immune cell (DC and T cell) function and differentiation. Some of the natural compounds, their exact signaling pathways still awaiting elucidation, may be used as novel adjuvants for innovative vaccination approaches, others appear to be strong immunosuppressants. The study of meta-MAMPs may not only comprise the first step into fundamentally novel therapies against infectious / inflammatory disorders, but will also contribute to our current knowledge on the regulation of immune cell fate and function.

Publications

Immunosuppressive mechanisms during infections

With our DEREG model we have significantly contributed to the understanding of T cell biology, particularly the importance of Tregs in the control of immune responses during inflammatory processes. Still, our knowledge on how Tregs differentiate, suppress and how they are regulated in a microbe-rich microenvironment, such as the site of infection or in the presence of commensal bacteria, is in its infancy. Moreover, manipulation of T cell immunity as a therapeutic strategy remains an uphill challenge and a central theme of our future efforts.

Publications

Therapeutic use of microbial immunomodulators

Minarrieta, L., Ghorbani, P., Sparwasser, T. and L. Berod. 2017. Metabolites: deciphering the molecular language between DCs and their environment. Semin Immunopathol 39(2): 177-198.

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.

Freitag J., L. Berod, T. Kamradt, T. Sparwasser. 2016. Immunometabolism and autoimmunity. Immunol Cell Biol 94(10): 925-934

Arnold-Schrauf, C., L. Berod, and T. Sparwasser. 2015. Dendritic cell specific targeting of MyD88 signalling pathways in vivo. Eur J Immunol 45:32-39.

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

Schildknecht, A., S. Brauer, C. Brenner, K. Lahl, H. Schild, T. Sparwasser*, H.C. Probst*, and M. van den Broek*. 2010. FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells. Proc Natl Acad Sci U S A 107:199-203. *equally contributed

Gross, O., A. Gewies, K. Finger, M. Schafer, T. Sparwasser, C. Peschel, I. Forster, and J. Ruland. 2006. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 442:651-656.
Sparwasser, T., T. Miethke, G. Lipford, K. Borschert, H. Hacker, K. Heeg, and H. Wagner. 1997. Bacterial DNA causes septic shock. Nature 386:336-337.

Funding: DFG (SFB 900), Boehringer Ingelheim Fonds, DAAD, FAPESP - The São Paulo Research Foundation, Fundação para a Ciência e Tecnologia, Ciência sem fronteiras, Volkswagen Foundation (Israel/Germany), DZIF

Immunosuppressive mechanisms during infections

Berod L., Lahl K., Lochner M., Mayer C.T. and T. Sparwasser. Regulatory T Cells. 2017. in: Inflammation: from Molecular and Cellular Mechanisms to the Clinic (J.-M. Cavaillon, M. Singer, eds.), Wiley-VCH (accepted for publication)

Ohkura, N., M. Hamaguchi, H. Morikawa, K. Sugimura, A. Tanaka, Y. Ito, M. Osaki, Y. Tanaka, R. Yamashita, N. Nakano, J. Huehn, H.J. Fehling, T. Sparwasser, K. Nakai, and S. Sakaguchi. 2012. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity 37:785-799.

Lahl, K., C.T. Mayer, T. Bopp, J. Huehn, C. Loddenkemper, G. Eberl, G. Wirnsberger, K. Dornmair, R. Geffers, E. Schmitt, J. Buer, and T. Sparwasser. 2009. Nonfunctional regulatory T cells and defective control of Th2 cytokine production in natural scurfy mutant mice. J Immunol 183:5662-5672.

Zelinskyy, G., K. Dietze, T. Sparwasser, and U. Dittmer. 2009. Regulatory T cells suppress antiviral immune responses and increase viral loads during acute infection with a lymphotropic retrovirus. PLoS Pathog 5:e1000406

Lahl, K., C. Loddenkemper, C. Drouin, J. Freyer, J. Arnason, G. Eberl, A. Hamann, H. Wagner, J. Huehn, and T. Sparwasser. 2007. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med 204:57-63.

Funding: Wilhelm-Sander-Stiftung, COALITION, EU (Marie Curie ITN fellowship), HSBDR