Infectious diseases still represent a key global health problem. In Europe, lower respiratory tract infections caused for example by Streptococcus pneumoniae are a major cause of morbidity and mortality, despite the availability of vaccines against this pathogen. Additionally, the rise in infections with multi-resistant bacteria, e.g. Mycobacterium tuberculosis, represents a constant threat for our society. Under the roof of the Department of Medical Microbiology and Hygiene, researchers led by Univ.-Prof. Dr. Tim Sparwasser are investigating several key aspects of infection biology. This includes a better understanding of host-pathogen interactions and the mechanisms that activate and regulate the infection-induced immune response. In addition, they explore the genetic background and the molecular processes of infection-associated immune responses and, most importantly, they search for novel ways of modulating the immune response, which finally aims to translate the findings of this basic research into clinical applications.
Advances in modern medicine, specifically in the area of transplantation and intensive care have greatly enhanced life expectancies in western countries, but also lead to a recurrence of opportunistic (e.g. CMV and Candida) and hospital-acquired (e.g. Clostridium difficile) infections that pose serious problems to our medical system. Additional challenges of the ageing European society comprise autoimmunity and cancer. These main challenges share the common root cause of being inadequate T cell-driven immune responses.
Vaccinations are considered one of the biggest success stories in medicine and can guarantee long-term sustainability and efficiency. However, the identification of better adjuvants, particularly for T cell immunity, would address one of the largest unmet clinical needs. Novel vaccines, especially against extensively drug-resistant bacteria such as mycobacteria, remain a major challenge. A new approach rather than focusing on the pathogen itself is the concept of ‘immunomodulation’. The identification and characterization of novel microbiota-derived metabolites which directly influence the host’s immune reaction offer novel therapeutic ways to shorten chemotherapy or to reduce immunopathology in infection or inflammatory disease.
Solmaz G., Puttur F., Francozo M., Lindenberg M., Guderian M., Swallow M., Duhan V., Khairnar V., Kalinke U., Ludewig B., Clausen B. E., Wagner H., Lang K. S., Sparwasser T. D.. TLR7 Controls VSV Replication in CD169(+) SCS Macrophages and Associated Viral Neuroinvasion. Frontiers in Immunology. 2019; 10
Schmidleithner L., Thabet Y., Schoenfeld E., Koehne M., Sommer D., Abdullah Z., Sadlon T., Osei-Sarpong C., Subbaramaiah K., Copperi F., Haendler K., Varga T., Schanz O., Bourry S., Bassler K., Krebs W., Peters A. E., Baumgart A-K., Schneeweiss M., Klee K., Schmidt S. V., Nuessing S., Sander J., Ohkura N., Waha A., Sparwasser T., Wunderlich F. T., Foerster I., Ulas T., Weighardt H., Sakaguchi S., Pfeifer A., Blueher M., Dannenberg A. J., Ferreiros N., Muglia L. J., Wickenhauser C., Barry S. C., Schultze J. L., Beyer M.. Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction.Immunity. 2019; 50 (5): 1232
Hosp C., Beyersdorf N., Kranz S., Stoevesandt J., Goebeler M., Sparwasser T., Trautmann A., Kerstan A. IL-10 is the driving force for successful tolerance induction in specific immunotherapy. Experimental Dermatology. 2019; 28(3): E10-E11
Steel N., Faniyi A. A., Rahman S., Swietlik S., Czajkowska ?, Chan B. T., Hardgrave A., Steel A., Sparwasser T. D., Assas M. B., Grencis R. K., Travis M. A., Worthington J. J.. TGF-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice. PLOS Pathogens. 2019; 15(4)
Al Nabhani Z, Dulauroy S, Marques R, Cousu C, Al Bounny S, Déjardin F, Sparwasser T, Bérard M, Cerf-Bensussan N, Eberl G. A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult. Immunity. 2019 Mar 12.
Ahmetlić F, Riedel T, Hömberg N, Bauer V, Trautwein N, Geishauser A, Sparwasser T, Stevanović S, Röcken M, Mocikat R. Regulatory T Cells in an Endogenous Mouse Lymphoma Recognize Specific Antigen Peptides and Contribute to Immune Escape. Cancer Immunol Res. 2019 Mar 20.
Mamareli P, Kruse F, Friedrich C, Smit N, Strowig T, Sparwasser T, Lochner M (2019) Epithelium-specific MyD88 signaling, but not DCs or macrophages, control acute intestinal infection with Clostridium difficile. Eur J Immunol. 2019 Feb 25
Wang Y, Dembowsky K, Chevalier E, Stüve P, Korf-Klingebiel M, Lochner M, Napp LC, Frank H, Brinkmann E, Kanwischer A, Bauersachs J, Gyongyosi M, Sparwasser T, Wollert KC (2019) C-X-C Motif Chemokine Receptor 4 Blockade Promotes Tissue Repair After Myocardial Infarction by Enhancing Regulatory T Cell Mobilization and Immune-Regulatory Function. Circulation. 2019 Jan 30.
Serradell MC, Rupil LL, Martino RA, Prucca CG, Carranza PG, Saura A, Fernandez EA, Gargantini PR, Tenaglia AH, Pititi JP, Tonelli RR, Reinoso-Vizcaino N, Echenique J, Berod L, Piaggio E, Bellier B, Sparwasser T, Klatzmann D, Lujan, HD (2019) Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins. Nature Communications 10.
Paul-Heng M, Leong M, Cunningham E, Bunker DLJ, Bremner K, Wang Z, Wang C, Tay SS, McGuffog C, Logan GJ, Alexander IE, Hu M, Alexander SI, Sparwasser TD, Bertolino P, Bowen DG, Bishop GA, Sharland A (2018) Direct recognition of hepatocyte-expressed MHC class I alloantigens is required for tolerance induction. JCI Insight 3(15).
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 28(3): 504--515.e7.
Divakaruni AS, Hsieh WY, Minarrieta L, Duong TN, Kim KKO, Desousa BR, Andreyev A.Y, Bowman CE, Caradonna K, Dranka BP, Ferrick DA, Liesa M, Stiles L, Rogers GW, Braas D, Ciaraldi TP, Wolfgang MJ, Sparwasser T, Berod L, Bensinger SJ, Murphy AN (2018) Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. Cell Metab 28(3): 490--503.e7.
Raud B, McGuire PJ, Jones RG, Sparwasser T, Berod L (2018) Fatty acid metabolism in CD8(+) T cell memory: Challenging current concepts. Immunol Rev 283(1): 213-231.
Akeus P, Szeponik L, Ahlmanner F, Sundström P, Alsen S, Gustavsson B, Sparwasser T, Raghavan S, Quiding-Jarbrink M (2018) Regulatory T cells control endothelial chemokine production and migration of T cells into intestinal tumors of APCmin/+ mice. Cancer Immunol Immunother 67(7): 1067-1077.
Velasquez L, Stüve P, Gentilini M, Swallow M, Bartel J, Lycke N, Barkan N, Martina M, Lujan H, Kalay H, Van Kooyk Y, Sparwasser T, Berod L (2018) Targeting mycobacterium tuberculosis antigens to dendritic cells via the DC-SIGN receptor induces strong Th1 immune responses.. Front Immunol 9 471.
Stüve P, Minarrieta L, Erdmann H, Arnold-Schrauf C, Swallow M, Guderian M, Krull F, Hölscher A, Ghorbani P, Behrends J, Abraham WR, Hölscher C, Sparwasser T, Berod L (2018) De novo fatty acid synthesis during mycobacterial infection is a prerequisite for the function of highly proliferative T cells, but not for dendritic cells or macrophages. Front Immunol 9 495.
Serradell MC, Gargantini PR, Saura A, Oms SR, Rupil LL, Berod L, Sparwasser T, Luján HD (2018) Cytokines, antibodies and histopathological profiles during Giardia infection and VSP-based vaccination. Infect Immuno 86(6).
Andreas N, Riemann M, Castro CN, Groth M, Koliesnik I, Engelmann C, Sparwasser T, Kamradt T, Haenold R, Weih F (2018) A new RelB-dependent CD117+ CD172a+ murine dendritic cell subset preferentially induces Th2 differentiation and supports airway hyperresponses in vivo. Eur J Immunol 48(6): 923-936.
Alissafi T, Kourepini E, Simoes DCM, Paschalidis N, Aggelakopoulou M, Sparwasser T, Boon L, Hammad H, Lambrecht BN, Panoutsakopoulou V (2018) Osteopontin Promotes Protective Antigenic Tolerance against Experimental Allergic Airway Disease. j Immunol 200(4): 1270-1282.
Singpiel A, Kramer J, Maus R, Stolper J, Bittersohl LF, Gauldie J, Kolb M, Welte T, Sparwasser T, Maus UA (2018) Adenoviral vector-mediated GM-CSF gene transfer improves anti-mycobacterial immunity in mice - role of regulatory T cells. Immunobiology 223(3): 331-341.
Semitekolou M, Morianos I, Banos A, Konstantopoulos D, Adamou-Tzani M, Sparwasser T, Xanthou G (2018) Dendritic cells conditioned by activin-A-induced regulatory T cells exhibit enhanced tolerogenic properties and protect against experimental asthma. J Allergy Clin Immunol 141(2): 671-684e7.