We study the host response to infection

Evolution has equipped organisms with sophisticated tools that can prevent or limit the impact of infectious disease and that directly target and destroy pathogenic microorganisms after infection. These defense mechanisms are referred to as Avoidance, Disease Tolerance and Resistance, respectively. In our group we focus on two aspects of the host response to infection: innate immunity affording resistance and mechanisms that preserve parenchymal functionality and integrity affording Disease Tolerance to infection.

In the field of Innate Immunity, we study long term and prevailing adaptive responses to sequential inflammatory stress with a special emphasis on innate immune training. While the well-known effects of LPS tolerance decreases subsequent immune responses, innate immune training leads to enhanced immunity upon restimulation. We have recently shown that also host-derived alarmins, such as the iron-containing molecule heme, impose long-lasting adaptation on the cellular and organismal level regulating the inflammatory reaction and disease severity to subsequent bacterial sepsis.

In the field of Disease Tolerance, we study mechanisms that maintain organ function in severe infections with a special emphasis on the molecular pathogenesis of the sepsis, that is the worse course of infectious disease. We specifically investigate adaptive and maladaptive host metabolic responses triggered during sepsis in order to understand mechanisms for new therapeutic strategies to ensure survival and organ integrity during sepsis.

We apply state-of-the-art techniques in immunology, genome engineering (e.g. using CRISPR-Cas9) cell biology and molecular biology, in vivo and in vitro infection models, metabolic cages and systems biology approaches such as transcriptomics, targeted metabolomics and single cell analysis and single nuclei ATAC sequencing, ChIP sequencing.

The group is part of the European Group to Study the Immunology of Sepsis (EGIS) and the wiggers-bernard initiative.

Our research group has a joint a joint affiliation with Jena University Hospital and the HKI. The Principial Investigator also works a senior attending physician at the Institute for Infectious Disease and Infection Control.

Team

Sebastian Weis
Head

Clinical studies

The joint affiliation of the group with the Jena University Hospital and the work as senior attending physician of the PI allows to run and participate in clinical trials. Currently the group is directly involved or is running the following clinical studies:

Publications

Bahrs C, Schönherr C, Panning M, Rose N, Dähne T, Hagel S, Weis S, Rupp J, Rohde G, Witzenrath M, Pletz MW (2024) Frequency and clinical significance of Herpes simplex virus type 1/2 reactivation in adult patients with mild to moderately severe community-acquired pneumonia: a multicentre cohort study. Infection , 1-7.
Giamarellos-Bourboulis EJ, Aschenbrenner AC, Bauer M, Bock C, Calandra T, Gat-Viks I, Kyriazopoulou E, Lupse M, Monneret G, Pickkers P, Schultze JL, van der Poll T, van de Veerdonk FL, Vlaar APJ, Weis S, Wiersinga WJ, Netea MG (2024) The pathophysiology of sepsis and precision-medicine-based immunotherapy. Nat Immunol 25(1), 19-28. (Review)
Kaasch AJ, López-Cortés LE, Rodríguez-Baño J, Cisneros JM, Dolores Navarro M, Fätkenheuer G, Jung N, Rieg S, Lepeule R, Coutte L, Bernard L, Lemaignen A, Kösters K, MacKenzie CR, Soriano A, Hagel S, Fantin B, Lafaurie M, Talarmin JP, Dinh A, Guimard T, Boutoille D, Welte T, Reuter S, Kluytmans J, Martin ML, Forestier E, Stocker H, Vitrat V, Tattevin P, Rommerskirchen A, Noret M, Adams A, Kern WV, Hellmich M, Seifert H (2024) Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial. Lancet Infect Dis 24(5), 523-534.