Regulation of neutrophils through thrombospondin- 1 in chronic urinary tract infection
Chronic urinary tract infections (cUTI) cause persistent neutrophil recruitment, tissue damage, and kidney fibrosis. Neutrophils clear bacteria but also exacerbate injury, promoting fibrosis. Thrombospondin- 1 (TSP1), a multifunctional extracellular matrix glycoprotein, interacts with neutrophils via MMP2, MMP9, and elastase, and regulates active TGF-β1 release, influencing neutrophil polarization and fibrotic processes. Thus, TSP1 may be a key environmental factor regulating neutrophil and fibrosis. Using experimental models, human samples, and advanced technologies, we investigate TSP1's role in neutrophil polarization, tissue microenvironment interactions, and renal fibrosis in cUTI.
Team
Publications
Divergent Granulopoiesis at Extramedullary Sites Safeguards Antibacterial Host DefenseSilvestre-Roig, C.; Chevre, R.; Farjia, M.; Bender, A.; Vöcking, L. M.; Richter, M.; Hageb, A.; Suerdieck, V.; Arenas Cerro, F. J.; Braster, Q.; Guzman, M.; Sintes, J.; Sharma, S.; Lemnitzer, P.; Tulotta, C.; Börgeling, Y.; Herrero-Cervera, A.; Flueter, H.; Reinartz Groba, S. N.; Ahern, D.; Osei-Sarpong, C.; Zimmer, R.; Alonso-Gonzalez, N.; Ortega, E.; Lienenklaus, S.; Kalinke, U.; Ludwig, S.; Engel, D. R.; Rosenbauer, F.; Monaco, C.; Dersch, P.; Kibler, A.; Cerutti, A.; Chavakis, T.; Benedito, R.; Hidalgo, A.; Jablonska, J.; Palomino-Segura, M.; Soehnlein, O.
2026 Sci Immunol
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Interleukin-1α Alters Megakaryocyte Maturation, Promotes Emperipolesis, and Induces a Distinct Proteomic ProfileKolman, R.; Voß, H.; Bertović, I.; Peradinović, J.; Munitić, I.; Engel, D. R.; Shevchuk, O.; Jurak Begonja, A.
2026 J. Thromb. Haemost
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Astrocytic PIEZO Activation by Heartbeat Sound Promotes Extracellular Matrix and Maturation in Human Brain OrganoidsFerreira Oliveira, A.; Rambow, F.; Makhzami, S.; Nikolaev, Y. A.; Novak, A.; Shevchuk, O.; Voss, H.; Engel, D. R.; Schult, P. A.; Pillath-Eilers, M.; Kaltwasser, B.; Brockmeier, U.; Kleinschnitz, C.; Hermann, D. M.; Dzyubenko, E.
2025 bioRxiv
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TSP1/TGF-Β1 Drives Arachidonic Acid Metabolism to Orchestrate Neutrophil SwarmingWidera, L.; Spangenberg, P.; Siemes, D.; Bessler, S.; Bottek, J.; Voss, H.; Novak, A.; Hueser, D.; Richter, M.; Potthoff, A.; Siebels, B.; Moritz, M.; Gocke, A.; Thiebes, S.; Tautges, S.; Chavakis, T.; Jablonska, J.; Lämmermann, T.; Gunzer, M.; Schlüter, H.; Hahn, J.; Grüneboom, A.; Soehnlein, O.; Dreisewerd, K.; Soltwisch, J.; Shevchuk, O.; Engel, D. R.
2025 bioRxiv
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G-CSF/NAMPT Signaling Drives Neutrophil Dysfunction and Enhances Bacterial Infection Susceptibility in Cancer PatientsPylaeva, E.; Tollrian, L.; Riedesel, J.; Shevchuk, O.; Thiel, I.; Ozel, I.; Kabankova, N.; Voß, H.; Siebels, B.; Schlüter, H.; Haist, C.; Hanenberg, H.; Mattheis, S.; Kürten, C.; Sperandio, M.; Kehrmann, J.; Engel, D. R.; Lang, S.; Jablonska, J.
2025 Nat Commun
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SCAMP3 Is Essential for Proper Formation and Function of Neutrophil GranulesBader, A.; Gao, J.; Reiter, N.; Siemes, D.; Zehrer, A.; Wei, X.; Hepper, I.; de Vega Gómez, E.; Schmid, B.; Forné, I.; Engel, D. R.; Walzog, B.; Maier-Begandt, D.
2025 J Leukoc Biol
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A Reference Database Enabling In-Depth Proteome and PTM Analysis of Mouse Immune CellsSiemes, D.; Voss, H.; Benvenuti, F.; Simoncello, F.; Kopczynski, D.; Siebels, B.; Schlüter, H.; Kollipara, L.; Sickmann, A.; Engel, D. R.; Shevchuk, O.
2025 Sci Data
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Inhibition of Tumour Necrosis Factor Alpha by Etanercept Attenuates Shiga Toxin-Induced Brain PathologyChrist, R.; Siemes, D.; Zhao, S.; Widera, L.; Spangenberg, P.; Lill, J.; Thiebes, S.; Bottek, J.; Borgards, L.; Pinho, A. G.; Silva, N. A.; Monteiro, S.; Jorch, S. K.; Gunzer, M.; Siebels, B.; Voss, H.; Schlüter, H.; Shevchuk, O.; Chen, J.; Engel, D. R.
2025 J Neuroinflammation
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msiFlow: automated workflows for reproducible and scalable multimodal mass spectrometry imaging and microscopy data analysisSpangenberg, P.; Bessler, S.; Widera, L.; Bottek, J.; Richter, M.; Thiebes, S.; Siemes, D.; Krauß, S. D.; Migas, L. G.; Kasarla, S. S.; Phapale, P.; Kleesiek, J.; Führer, D.; Moeller, L. C.; Heuer, H.; Van de Plas, R.; Gunzer, M.; Soehnlein, O.; Soltwisch, J.; Shevchuk, O.; Dreisewerd, K.; Engel, D. R.
2025 Nat Commun
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Stroke and Myocardial Infarction Induce Neutrophil Extracellular Trap Release Disrupting Lymphoid Organ Structure and Immunoglobulin SecretionTuz, A. A.; Ghosh, S.; Karsch, L.; Ttoouli, D.; Sata, S. P.; Ulusoy, Ö.; Kraus, A.; Hoerenbaum, N.; Wolf, J.-N.; Lohmann, S.; Zwirnlein, F.; Kaygusuz, V.; Lakovic, V.; Tummes, H.-L.; Beer, A.; Gallert, M.; Thiebes, S.; Qefalia, A.; Cibir, Z.; Antler, M.; Korste, S.; Haj Yehia, E.; Michel, L.; Rassaf, T.; Kaltwasser, B.; Abdelrahman, H.; Mohamud Yusuf, A.; Wang, C.; Yin, D.; Haeusler, L.; Lueong, S.; Richter, M.; Engel, D. R.; Stenzel, M.; Soehnlein, O.; Frank, B.; Solo-Nomenjanahary, M.; Ho-Tin-Noé, B.; Siveke, J. T.; Totzeck, M.; Hoffmann, D.; Grüneboom, A.; Hagemann, N.; Hasenberg, A.; Desilles, J.-P.; Mazighi, M.; Sickmann, A.; Chen, J.; Hermann, D. M.; Gunzer, M.; Singh, V.
2024 Nat Cardiovasc Res
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Scientific Advances in Understanding the Pathogenesis, Diagnosis, and Prevention of Urinary Tract Infection in the Past 10 YearsEngel, D. R.; Wagenlehner, F. M. E.; Shevchuk, O.
2024 Infect Dis Clin North Am
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Neutrophils - Biology and DiversityMaier-Begandt, D.; Alonso-Gonzalez, N.; Klotz, L.; Erpenbeck, L.; Jablonska, J.; Immler, R.; Hasenberg, A.; Mueller, T. T.; Herrero-Cervera, A.; Aranda-Pardos, I.; Flora, K.; Zarbock, A.; Brandau, S.; Schulz, C.; Soehnlein, O.; Steiger, S.; the TRR332 consortium.
2023 Nephrol Dial Transplant
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Comparative transcriptomic and proteomic signature of lung alveolar macrophages reveals the integrin CD11b as a regulatory hub during pneumococcal pneumonia infectionZec, K.; Thiebes, S.; Bottek, J.; Siemes, D.; Spangenberg, P.; Trieu, D. V.; Kirstein, N.; Subramaniam, N.; Christ, R.; Klein, D.; Jendrossek, V.; Loose, M.; Wagenlehner, F.; Jablonska, J.; Bracht, T.; Sitek, B.; Budeus, B.; Klein-Hitpass, L.; Theegarten, D.; Shevchuk, O.; Engel, D. R.
2023 Front Immunol
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Rapid and Fully Automated Blood Vasculature Analysis in 3D Light-Sheet Image Volumes of Different OrgansSpangenberg, P.; Hagemann, N.; Squire, A.; Förster, N.; Krauß, S. D.; Qi, Y.; Yusuf, A. M.; Wang, J.; Grüneboom, A.; Kowitz, L.; Korste, S.; Totzeck, M.; Cibir, Z.; Tuz, A. A.; Singh, V.; Siemes, D.; Struensee, L.; Engel, D. R.; Ludewig, P.; Nascentes Melo, L. M.; Helfrich, I.; Chen, J.; Gunzer, M.; Hermann, D. M.; Mosig, A.
2023 Cell Reports Methods
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Non-Invasive Mapping of Systemic Neutrophil Dynamics upon Cardiovascular InjuryBouvain, P.; Ding, Z.; Kadir, S.; Kleimann, P.; Kluge, N.; Tiren, Z.-B.; Steckel, B.; Flocke, V.; Zalfen, R.; Petzsch, P.; Wachtmeister, T.; John, G.; Subramaniam, N.; Krämer, W.; Strasdeit, T.; Mehrabipour, M.; Moll, J. M.; Schubert, R.; Ahmadian, M. R.; Bönner, F.; Boeken, U.; Westenfeld, R.; Engel, D. R.; Kelm, M.; Schrader, J.; Köhrer, K.; Grandoch, M.; Temme, S.; Flögel, U.
2023 Nature Cardiovascular Research
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