Host-pathogen interactions in neutrophils
Major human pathogens adapted to the human host for millennia and developed intricate mechanisms to circumvent the immune defence rendering them a global health burden. We have identified an altered proteomic signature in neutrophils induced by Mycobacterium tuberculosis or Helicobacter pylori compared to non-human-adapted pathogens and non-pathogenic bacteria. I hypothesize that human-adapted pathogens induce unique proteomic alterations in neutrophils to evade their own killing and we evaluate these specifically altered proteins for their potential as new therapeutic targets. Using CRISPR/Cas9-engineered induced pluripotent stem (iPS) cell-derived neutrophils and zebrafish larvae, we assess how deficiency or overexpression of the identified proteins impact bacterial killing. We analyse whether the identified proteins are similarly regulated in samples from infected humans as well as in individuals from risk groups such as young children, elderly or diabetic patients. Finally, we elucidate the pathophysiological mechanisms how regulation of protein expression is achieved and how this promotes survival of human-adapted pathogens.
Team
Publications
IL-1α Drives a Tumor-Stroma-Neutrophil Axis through Inflammatory Fibroblast Activation in Head and Neck CancerHanschmann, E.-M.; Bruderek, K.; Hofmann-Vega, F.; Schmidt, M.; Budeus, B.; Oberlies, W.; Wei, X.; Richter, M.; Lemm, S.; Szlachetko, J. A.; Ryan, S.; Bader, A.; Daser, A.; Lang, S.; Maier-Begandt, D.; Hussain, T.; Soehnlein, O.; Brandau, S.
2026 bioRxiv
|
Mutations in VPS18 Lead to a Neutrophil Maturation Defect Associated with Disturbed Vesicle HomeostasisGao, J.; Bader, A.; Linder, M. I.; Cheng, J.; Richter, M.; Da Costa, R.; Zehrer, A.; Mitt, K.; Popper, B.; Meissner, F.; Wei, X.; De Vega Gómez, E.; Tatematsu, M.; Rohlfs, M.; Frenz-Wiessner, S.; Kiziltug, M.; Somekh, I.; Yacobovich, J.; Steinberg-Shemer, O.; Somech, R.; Soehnlein, O.; Schmid, B.; Klein, C.; Walzog, B.; Maier-Begandt, D.
2026 Cell Death Dis
|
The Nuclear Receptor NR4A1 Serves as a Neutrophil-Intrinsic Regulator Mitigating Stroke SeverityStrecker, J.-K.; Schmidt, Y.; Liebmann, M.; Walter, C.; Roth, S.; Aleth, H.; Börsch, A.-L.; Schmidt-Pogoda, A.; Beuker, C.; Yusuf, A. M.; Revenstorff, J.; Osei-Sarpong, C.; Krafft, L.; Schwarze, A.-S.; Heming, M.; Richter, M.; Kuhlmann, T.; Hucke, S.; Heming, J.-N.; Hansen, U.; Hagemann, N.; Bader, A.; Gao, J.; Walzog, B.; Maier-Begandt, D.; Chevre, R.; Hanschmann, E.-M.; Lücke, M.; Sommer, C.; Hermann, D. M.; Roth, J.; Thomas, C.; Meyer Zu Hörste, G.; Gunzer, M.; Vogl, T.; Zarbock, A.; Rosenbauer, F.; Silvestre-Roig, C.; Söhnlein, O.; Klotz, L.; Minnerup, J.
2025 bioRxiv
|
Sex Differences in Neutrophil BiologyRichter, M.; Maier-Begandt, D.; Jablonska, J.; Silvestre-Roig, C.
2025 J Leukoc Biol
|
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
|
Cytosolic S100A8/A9 Promotes Ca2+ Supply at LFA-1 Adhesion Clusters during Neutrophil RecruitmentNapoli, M.; Immler, R.; Rohwedder, I.; Lupperger, V.; Pfabe, J.; Gonzalez Pisfil, M.; Yevtushenko, A.; Vogl, T.; Roth, J.; Salvermoser, M.; Dietzel, S.; Slak Rupnik, M.; Marr, C.; Walzog, B.; Sperandio, M.; Pruenster, M.
2024 Elife
|
Novel Multiphoton Intravital Imaging Enables Real-Time Study of Helicobacter Pylori Interaction with Neutrophils and Macrophages in the Mouse StomachIshikawa-Ankerhold, H.; Busch, B.; Bader, A.; Maier-Begandt, D.; Dionisio, F.; Namineni, S.; Vladymyrov, M.; Harrison, U.; van den Heuvel, D.; Tomas, L.; Walzog, B.; Massberg, S.; Schulz, C.; Haas, R.
2024 PLoS Pathog
|
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
|
A20 and the Noncanonical NF-κB Pathway Are Key Regulators of Neutrophil Recruitment during Fetal OntogenyRohwedder, I.; Wackerbarth, L. M.; Heinig, K.; Ballweg, A.; Altstätter, J.; Ripphahn, M.; Nussbaum, C.; Salvermoser, M.; Bierschenk, S.; Straub, T.; Gunzer, M.; Schmidt-Supprian, M.; Kolben, T.; Schulz, C.; Ma, A.; Walzog, B.; Heinig, M.; Sperandio, M.
2023 JCI Insight
|
Human Genetic Defects in SRP19 and SRPRA Cause Severe Congenital Neutropenia with Distinctive Proteome ChangesLinder, M. I.; Mizoguchi, Y.; Hesse, S.; Csaba, G.; Tatematsu, M.; Łyszkiewicz, M.; Zietara, N.; Jeske, T.; Hastreiter, M.; Rohlfs, M.; Liu, Y.; Grabowski, P.; Ahomaa, K.; Maier-Begandt, D.; Schwestka, M.; Pazhakh, V.; Isiaku, A.; Briones Miranda, B.; Blombery, P.; Saito, M. K.; Rusha, E.; Alizadeh, Z.; Pourpak, Z.; Kobayashi, M.; Rezaei, N.; Unal, E.; Hauck, F.; Drukker, M.; Walzog, B.; Rappsilber, J.; Zimmer, R.; Lieschke, G. J.; Klein, C.
2023 Blood
|