Metabolic priming of monocytes during inflammation in vivo

Principal investigators: Johannes Roth, Michael Schäfers
Project number: CRC 1450 C01
Project term: 01/2021–12/2028

During systemic inflammation, shifts in metabolism lead to a secondary immune tolerance with a life-threatening defective antimicrobial defence. We demonstrated significant metabolic alterations during tolerance in monocytes. We will now target specific metabolic pathways in monocytes to analyse functional consequences. We will use metabolic radiotracers and innovative tracking strategies to confirm their relevance in infections and sterile inflammation. Our final goal is the identification of metabolites which could be used as innovative tracers for imaging specific disease stages or therapeutic targets for inflammation.

Team

Principal investigators

Project members

Publications

The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.

2024

Höffgen KS, Dabel J, Konken CP, Depke DA, Hermann S, Dörner W, Schelhaas S, Schäfers M, Mootz HD. Combining poly-epitope MoonTags and labeled nanobodies for signal amplification in cell-specific PET imaging in vivo. Nucl Med Biol 2024;136-137: 108937. Abstract
Ventura D, Dittmann M, Büther F, Schäfers M, Rahbar K, Hescheler D, Claesener M, Schindler P, Riemann B, Seifert R, Roll W. Diagnostic Performance of [(18)F]TFB PET/CT Compared with Therapeutic Activity [(131)I]Iodine SPECT/CT and [(18)F]FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma. J Nucl Med 2024;65: 192-198. Abstract

2023

Hoffmann E, Schache D, Höltke C, Soltwisch J, Niland S, Krähling T, Bergander K, Grewer M, Geyer C, Groeneweg L, Eble JA, Vogl T, Roth J, Heindel W, Maus B, Helfen A, Faber C, Wildgruber M, Gerwing M, Hoerr V. Multiparametric chemical exchange saturation transfer MRI detects metabolic changes in breast cancer following immunotherapy. J Transl Med 2023;21: 577. Abstract
Ludwig N, Thörner-van Almsick J, Mersmann S, Bardel B, Niemann S, Chasan AI, Schäfers M, Margraf A, Rossaint J, Kahl BC, Zarbock A, Block H. Nuclease activity and protein A release of Staphylococcus aureus clinical isolates determine the virulence in a murine model of acute lung infection. Front. Immunol. 2023;14Abstract
Pruenster M, Immler R, Roth J, Kuchler T, Bromberger T, Napoli M, Nussbaumer K, Rohwedder I, Wackerbarth LM, Piantoni C, Hennis K, Fink D, Kallabis S, Schroll T, Masgrau-Alsina S, Budke A, Liu W, Vestweber D, Wahl-Schott C, Roth J, Meissner F, Moser M, Vogl T, Hornung V, Broz P, Sperandio M. E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/S100A9 release from neutrophils via transient gasdermin D pore formation. Nat Immunol 2023;24: 2021-2031. Abstract
Roll W, Faust A, Hermann S, Schäfers M. Infection Imaging: Focus on New Tracers?. J Nucl Med 2023;64: 59s-67s. Abstract
Song J, Deshpande T, Zhang X, Hannocks M-J, Lycke N, Cardell SL, Sorokin L. The extracellular matrix of lymph node reticular fibers modulates follicle border interactions and germinal center formation. iScience 2023;26: 106753. Abstract
von Wulffen M, Luehrmann V, Robeck S, Russo A, Fischer-Riepe L, van den Bosch M, van Lent P, Loser K, Gabrilovich DI, Hermann S, Roth J, Vogl T. S100A8/A9-alarmin promotes local myeloid-derived suppressor cell activation restricting severe autoimmune arthritis. Cell Rep 2023;42: 113006. Abstract

2022

Bobe S, Beckmann D, Klump DM, Dierkes C, Kirschnick N, Redder E, Bauer N, Schäfers M, Erapaneedi R, Risse B, van de Pavert SA, Kiefer F. Volumetric imaging reveals VEGF-C-dependent formation of hepatic lymph vessels in mice. Front Cell Dev Biol 2022;10: 949896. Abstract
Honold L, Austrup M, Faust A, Konken CP, Schwegmann K, Zinnhardt B, Daniliuc CG, Haufe G, Schäfers M, Kopka K, Hermann S. Towards Optimized Bioavailability of (99m)Tc-Labeled Barbiturates for Non-invasive Imaging of Matrix Metalloproteinase Activity. Mol Imaging Biol 2022;24: 434-443. Abstract
Rösner L, Konken CP, Depke DA, Rentmeister A, Schäfers M. Covalent labeling of immune cells. Curr Opin Chem Biol 2022;68: 102144. Abstract
Russo A, Schürmann H, Brandt M, Scholz K, Matos ALL, Grill D, Revenstorff J, Rembrink M, von Wulffen M, Fischer-Riepe L, Hanley PJ, Häcker H, Prünster M, Sanchez-Madrid F, Hermann S, Klotz L, Gerke V, Betz T, Vogl T, Roth J. Alarming and Calming: Opposing Roles of S100A8/S100A9 Dimers and Tetramers on Monocytes. Adv Sci (Weinh) 2022: e2201505. Abstract
Thomas K, Zondler L, Ludwig N, Kardell M, Lüneburg C, Henke K, Mersmann S, Margraf A, Spieker T, Tekath T, Velic A, Holtmeier R, Hermann J, Jankowski V, Meersch M, Vestweber D, Westphal M, Roth J, Schäfers MA, Kellum JA, Lowell CA, Rossaint J, Zarbock A. Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells. JCI Insight 2022;7Abstract

2021

Chaoprasid P, Lukat P, Mühlen S, Heidler T, Gazdag E-M, Dong S, Bi W, Rüter C, Kirchenwitz M, Steffen A, Jänsch L, Stradal TEB, Dersch P, Blankenfeldt W. Crystal structure of bacterial cytotoxic necrotizing factor CNF(Y) reveals molecular building blocks for intoxication. Embo J 2021;40: e105202. Abstract
Depke DA, Konken CP, Rösner L, Hermann S, Schäfers M, Rentmeister A. A novel (18)F-labeled clickable substrate for targeted imaging of SNAP-tag expressing cells by PET in vivo. Chem Commun (Camb) 2021;57: 9850-9853. Abstract

2020

Dittmann M, Gonzalez Carvalho JM, Rahbar K, Schäfers M, Claesener M, Riemann B, Seifert R. Incremental diagnostic value of [(18)F]tetrafluoroborate PET-CT compared to [(131)I]iodine scintigraphy in recurrent differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2020;47: 2639-2646. Abstract
Fischer-Riepe L, Daber N, Schulte-Schrepping J, Veras De Carvalho BC, Russo A, Pohlen M, Fischer J, Chasan AI, Wolf M, Ulas T, Glander S, Schulz C, Skryabin B, Wollbrink Dipl-Ing A, Steingraeber N, Stremmel C, Koehle M, Gärtner F, Vettorazzi S, Holzinger D, Gross J, Rosenbauer F, Stoll M, Niemann S, Tuckermann J, Schultze JL, Roth J, Barczyk-Kahlert K. CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow. J Allergy Clin Immunol 2020;146: 1137-1151. Abstract

2019

Fischer J, Walter C, Tönges A, Aleth H, Jordao MJC, Leddin M, Gröning V, Erdmann T, Lenz G, Roth J, Vogl T, Prinz M, Dugas M, Jacobsen ID, Rosenbauer F. Safeguard function of PU1 shapes the inflammatory epigenome of neutrophils. Nat Immunol 2019;20: 546-558. Abstract
Freise N, Burghard A, Ortkras T, Daber N, Imam Chasan A, Jauch S-L, Fehler O, Hillebrand J, Schakaki M, Rojas J, Grimbacher B, Vogl T, Hoffmeier A, Martens S, Roth J, Austermann J. Signaling mechanisms inducing hyporesponsiveness of phagocytes during systemic inflammation. Blood 2019;134: 134-146. Abstract

2018

Heming M, Gran S, Jauch S-L, Fischer-Riepe L, Russo A, Klotz L, Hermann S, Schäfers M, Roth J, Barczyk-Kahlert K. Peroxisome Proliferator-Activated Receptor-γ Modulates the Response of Macrophages to Lipopolysaccharide and Glucocorticoids. Front Immunol 2018;9: 893. Abstract
Vogl T, Stratis A, Wixler V, Völler T, Thurainayagam S, Jorch SK, Zenker S, Dreiling A, Chakraborty D, Fröhling M, Paruzel P, Wehmeyer C, Hermann S, Papantonopoulou O, Geyer C, Loser K, Schäfers M, Ludwig S, Stoll M, Leanderson T, Schultze JL, König S, Pap T, Roth J. Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation. J Clin Invest 2018;128: 1852-1866. Abstract

2017

Thunemann M, Schörg BF, Feil S, Lin Y, Voelkl J, Golla M, Vachaviolos A, Kohlhofer U, Quintanilla-Martinez L, Olbrich M, Ehrlichmann W, Reischl G, Griessinger CM, Langer HF, Gawaz M, Lang F, Schäfers M, Kneilling M, Pichler BJ, Feil R. Cre/lox-assisted non-invasive in vivo tracking of specific cell populations by positron emission tomography. Nat Commun 2017;8: 444. Abstract
Ulas T, Pirr S, Fehlhaber B, Bickes MS, Loof TG, Vogl T, Mellinger L, Heinemann AS, Burgmann J, Schöning J, Schreek S, Pfeifer S, Reuner F, Völlger L, Stanulla M, von Köckritz-Blickwede M, Glander S, Barczyk-Kahlert K, von Kaisenberg CS, Friesenhagen J, Fischer-Riepe L, Zenker S, Schultze JL, Roth J, Viemann D. S100-alarmin-induced innate immune programming protects newborn infants from sepsis. Nat Immunol 2017;18: 622-632. Abstract