Immunopathogenesis and organ dysfunction

Leitung

Prof. Dr. med. Christian Bode

0228-281-14119
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Focus of research

Molecular and cellular pathomechanisms of the immune response in the context of inflammatory diseases including Systemic Inflammatory Response Syndrome (SIRS), sepsis or ARDS are central questions of our scientific work. In a translational approach, we investigate the regulation of the innate immune response after the recognition of danger and pathogen-associated molecular patterns (DAMPs and PAMPs) and the inhibition of the activated signaling pathways. A particular focus here is on understanding the individual immune reaction in order to treat organ failure in the context of the heterogeneous syndromes such as ARDS in a personalized manner.

We recently demonstrated in a reverse-translational approach that patients with direct (pulmonal) ARDS possess substantially higher levels of the inflammasome-derived cytokines IL-1β and IL-18 in their lungs than those with indirect (nonpulmonary) ARDS. In experimental acute lung injury, tetracycline significantly diminished lung injury and pulmonary inflammation by selectively inhibiting caspase-1-dependent IL-1β and IL-18 production, leading to improved survival. Finally, we could show that tetracycline also reduced the production of IL-1β and IL-18 by alveolar leukocytes from patients with direct ARDS. (Am J Respir Crit Care Med 2021; 204(1):53-63)

We are further interested how the metabolism influences the host immune response in ARDS. In a German Research foundation (DFG)-supported project, we revealed together with Prof. C. Wilhelm (Institute of Clinical Chemistry and Clinical Pharmacology) that patients with SARS-CoV-2- but not influenza-induced ARDS have an impaired production of ketone bodies (BHB). BHB promotes the survival and the production of Interferon-g from CD4+ T cells. We uncovered that BHB provides an alternative carbon source to fuel oxidative phosphorylation (OXPHOS) and the production of bioenergetic amino acids and glutathione, which is important for maintaining the redox balance. T cells from patients with COVID-19 ARDS were exhausted and skewed towards glycolysis, but can be metabolically reprogrammed by BHB to perform OXPHOS, thereby increasing their functionality. Finally, we found that ketogenic diet (KD) reduced pulmonary fibrosis, a feature particular pronounced in COVID-19 ARDS and delivery of BHB as ketone ester drink reduces the mortality of SARS-CoV-2 infected mice (Nature 2022, 609(7928):801-807).

Clinical Research

A major clinical research interest focuses on blood purification in septic shock. In a prospective bicentric RCT with the Hannover Medical School (Prof. S. David and PD K. Stahl), we could demonstrate that early therapeutic plasma exchange (TPE) improves hemodynamics in patients with severe septic shock (Intensive Care Med. 2021; 47, 352-354). Current research focuses on the effect of TPE on the inflammatory response in patients in various inflammatory conditions.

Furthermore, we want to understand the aging-related changes of the immune system and its contribution to the postoperative morbidity and mortality in the Elderly. Therefore, we currently perform a pilot study with an interdisciplinary consortium (POPIMAGE study group) to explore the immune system in the elderly undergoing major surgery. Participants will be evaluated for acute and long-term outcomes, including all-cause mortality, physical and cognitive function. To assess the individual's immunobiography, participants will be characterized by inflammation biomarkers combined with immunophenotyping, functional assays, and (epi-) genomic analyses before and after surgery.

Personalized systems innate immunology during SIRS / Sepsis
Therapeutic plasma-exchange as an adjunctive strategy against septic shock
Modulation of the cGAS-STING pathway in systemic inflammation
Functional immunophenotyping of elderly patients undergoing major surgery to assess accelerated inflammaging and prediction of postoperative complications
Immundysfunction in ARDS subphenotypes

Leitung / Ansprechpartner inkl. Kontaktdaten

Prof. Dr. med. Christian Bode

0228-281-14119
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Mitarbeiter

Zhaorong Chen
Mario Fox
Philippe Kruse
Dr. Konrad Peukert
Dr. Andrea Sauer
Susanne Schulz
Dr. Lennart Wild

Doktorand*innen

cand. med. Enrico Cotalla
Caroline Feuerborn
cand. med. Lorena Müller
cand. med. Anna Rier
cand. med. Finn Schirmer

Das KAI-Fellowship richtet sich an unsere Assistenzärzt*innen, um sie in der Anfangsphase ihrer Karriere zu unterstützen. Dabei wird ein fester Anteil der Arbeitszeit für die Forschung genutzt. Das Programm startete 2022 und soll die Datengenerierung für eine spätere Drittmitteleinwerbung bzw. ein Stipendiat ermöglichen.

Förderumfang: Bis zu 0,7 TVÄ-Stelle, 6-12 Monate, Verlängerung möglich nach Reevaluation

Voraussetzungen: Ärztliche Mitarbeiter KAI, wisschenschaftliche Vorkenntnisse, definiertes Forschungsthema unter Betreuung eines qualifizierten Mitarbeiters, Intra- und extramurale Förderung derzeit nicht möglich

Antragsunterlagen: Vorhabenbeschreibung inkl. Arbeitsprogramm, Zeitplan, Genehmigungen, Erfolgsaussichten/Perspektive inkl. obligates Drittmittelantragskonzept (max. 2 Seiten)

To answer both basic and clinical research questions as precisely as possible, we have established with two other university hospitals the Bonn-Hanover-Zürich ARDS (BonHanZA)-Study group.

Prof. Dr. Christoph Wilhelm (Institut für Klinische Chemie und Klinische Pharmakologie, Universitätsklinikum Bonn)
Prof. Dr. Eicke Latz / Dr. Susanne Schmidt (Institut für Angeborene Immunität, Universitätsklinikum Bonn)
Prof. Dr. Sascha David (Institut für Intensivmedizin, Universitätsspital Zürich)
PD Dr. Klaus Stahl (Klinik für Gastroenterologie, Medizinische Hochschule Hannover)
Prof. Dr. Tobias Welte / Dr. Benjamin Seeliger (Klinik für Pulmonologie, Medizinische Hochschule Hannover)
PD Dr. Dennis Klinman (National Cancer Institute, NIH, USA)
PD Dr. Beate Kümmerer (Institut für Virologie, Universitätsklinikum Bonn)
Prof. Thorsten Brenner / Prof. Marc Berger (Klinik für Anästhesiologie, Universitätsklinikum Essen)
Dr. Silke Grumaz (Noscendo GmbH)
Dr. Andrew Aswani, MD, PhD, Critical Care Medicine and Anesthesia, Guy´s and St. Thomas´ NHS Foundation Trust, London, UK, and Santersus
PD Dr. Folkert Steinhagen (GFO Kliniken Bonn)

Karagiannis F*, Peukert K*, Surace L*, Michla M, Nikolka F, Fox M, Weiss P, Feuerborn C, Maier P, Schulz S, Al B, Seeliger B, Welte T, David S, Grondman I, de Nooijer AH, Pickkers P, Kleiner JL, Berger MM, Brenner T, Putensen C; Bonn COVIMMUNE Consortium, Kato H, Garbi N, Netea MG, Hiller K, Placek K*, Bode C*^#, Wilhelm C*^#. Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19. Nature 2022; 609(7928):801-807 (*contributed equally, ^# corresponding authors)
Stahl K*, Wand P*, Seeliger B, Wendel-Garcia P, Schmidt J, Schmidt B, Sauer A, Lehmann F, Budde U, Busch M, Wiesner O, Welte T, Haller H, Wedemeyer H, Putensen C, Hoeper M, Bode C*, David S*. Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock – results from a randomized controlled trial. Crit Care. 2022. 26(1):134 (*contributed equally)
Seeliger B*, Doebler M*, Hofmaenner D*, Wendel-Garcia P, Schuepbach R, Schmidt J, Welte T, Hoeper M, Gillmann H, Kuehn C, Ehrentraut S, Schewe JC, Putensen C, Stahl K*, Bode C*, David S*. Intracranial hemorrhages on extracorporeal membrane oxygenation: differences between coronavirus disease 2019 and other viral acute respiratory distress syndrome. Crit Care Med. 2022. 50(6);e526-e538. (*contributed equally)
Aramburu IV, Hoving D, Vernardis SI, Tin MCF, Ioannou M, Temkin MI, Vasconcelos NM, Demichev V, Helbig EH, Lippert L, Stahl K, White M, Radbruch H, Ihlow J, Horst D, Chiesa ST, Deanfield JE, David S, Bode C, Kurth F, Ralser M, Papayannopoulos. Functional proteomic profiling links deficient DNA clearance with increased mortality in individuals with severe COVID-19 pneumonia. Immunity 2022. Published Nov 16. Doi.org/10.1016/j.immuni.2022.11.007
Sauer A, Putensen C, Bode C. Immunomodulation by tetracyclines in the critical ill – an emerging treatment option? Crit Care. 2022; 26, 74
Peukert K, Fox M, Schulz S, Feuerborn C, Frede S, Putensen C, Wrigge H, Kümmerer BM, David S, Seeliger B, Welte T, Latz E, Klinman D, Wilhelm C, Steinhagen F, Bode C. Inhibition of Caspase-1 with Tetracycline Ameliorates Acute Lung Injury. Am J Respir Crit Care Med. 2021; 204(1): 53-63
Seeliger B*, Döbler M*, Friedrich R, Stahl K, Kühn C, Bauersachs J, Steinhagen F, Ehrentraut S, Schewe J, Putensen C, Welte T, Hoeper M, Tiede A, David S*, Bode C*. Comparison of anticoagulation strategies for veno-venous ECMO support in acute respiratory failure. Crit Care. 2021; 24(1):701. (*contributed equally)
Sauer A, Peukert K, Putensen C, Bode C. Antibiotics as immunomodulators: a potential pharmacologic approach for ARDS treatment. Europ Resp Review. 2021; 30(162):210093
David S*, Bode C*, Putensen C, Welte T, Stahl K, EXCHANGE study group. Adjuvant therapeutic plasma exchange in septic shock. Intensive Care Med. 2021; 47, 352-354 (*contributed equally).
Steinhagen F, Schmidt S, Schewe JC, Peukert K, Klinman DM, Bode C. Immunotherapy in sepsis - brake or accelerate? Pharmacol Ther. 2020; 208:107476.

Hugo-Schottmüller-Preis 2022 der deutschen Sepsis-Gesellschaft für Christian Bode
1.Preis freie Vorträge - experimentelle Studien. Peukert K., Feuerborn C., Sauer A., Fox M., Schulz S., Wilhelm C., Coburn M., Putensen C., Bode C.. Der Inflammasome-Caspase-1 Signalweg ist mit der Krankheitsschwere des Covid-19 ARDS assoziiert und wird durch Tetrazyklin inhibiert. 22. Hauptstadtkongress der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin 2022
Heinrich-Dräger-Preis für Intensivmedizin 2022 für Christian Bode
Forschungsstipendium der Fresenius-Stiftung auf den Wissenschaftlichen Arbeitstagen der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin 2022 für Konrad Peukert
1. Preis freie Vorträge - klinische Studien. Bode C., Peukert K., Fox M, Schewe J, Putensen C, Latz E, Steinhagen F. Differentielle Produktion inflammasomabhängiger Zytokine und deren Inhibition durch Tetrazyklin im humanen ARDS. 21. Hauptstadtkongress der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin 2019

1. Preis Posterpräsentationen – experimentelle Arbeiten. Peukert K., Fox M., Schulz S., Wilhelm C., Frede S., Latz E, Steinhagen F, Bode C. Tetrazyklin verbessert den akuten Lungenschaden durch Inhibition des NLRP3-Inflammasoms. 21. Hauptstadtkongress der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin 2019

1. Preis Einzelvortrag Gerok-Stipendium. Peukert K, Fox M, Frede S, Wilhelm C, Latz E, Steinhagen F, Bode C. Tetracycline alleviates acute lung injury by selective inhibition of caspase-1. 21. BONFOR-Symposium der medizinischen Fakultät der Universität Bonn 2019

1. Preis freie Vorträge - experimentelle Studien. Bode C., Überdiek B.,Hentschel V, Ehrentraut H, Boehm O, Knüfermann P, Baumgarten G. Immunmodulation durch Antibiotika: Rolle der Toll-like Rezeptoren. 11. Hauptstadtkongress der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin 2009

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