Research

We investigate the mechanisms of pulmonary immune responses and their regulation in infections with e.g. Streptococcus pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa and Klebsiella pneumoniae. Using established in vitro and in vivo models, we are studying how the immune system detects infections, how it combats intracellular bacteria, and how it controls infections with extracellular bacteria. Our goal is to better understand the immunological processes in the lung and their regulation.

Project-related publications

Ruiz-Moreno JS, Hamann L, Jin L, Sander LE, Puzianowska-Kuznickad M, Cambier JC, Witzenrath M, Suttorp N, Schumann RR, Opitz B, CAPNETZ Study Group. The cGAS/STING pathway detects Streptococcus pneumoniae but is dispensable for anti-pneumococcal defense in mice and humans. Infect Immun. 2018;86:e00849-17. https://doi.org/10.1128/iai.00849-17

Ruiz-Moreno JS, Hamann L, Shah JA, Verbon A, Mockenhaupt FP, Puzianowska-Kuznicka M, Naujoks J, Sander LE, Witzenrath M, Cambier JC, Suttorp N, Schumann RR, Jin L, Hawn TR, Opitz B, CAPNETZ Study Group. A common hypomorphic STING variant affects cGAS-dependent antibacterial defense and is associated with susceptibility to Legionnaires‘ disease in humans. PLOS Pathog. 2018;14:e1006829. https://doi.org/10.1371/journal.ppat.1006829

Witzenrath M, Pache F, Lorenz D, Koppe U, Schönrock S, Meixenberger K, Dorhoi A, Ma J, Holmes A, Trendelenburg G, Heimesaat MM, Bereswill S, van der Linden M, Tschopp J, Mitchell TJ, Suttorp N, Opitz B. The NLRP3 Inflammasome is Differentially Activated by Pneumolysin Variants and Contributes to Host Defense in Pneumococcal Pneumonia. J Immunol. 2011;187:434-40. https://doi.org/10.4049/jimmunol.1003143

Opitz B, van Laak V, Eitel J, Suttorp N. Innate immune recognition in infectious and non-infectious diseases of the lung. Am J Respir Crit Care Med. 2010;181:1294-309. https://doi.org/10.1164/rccm.200909-1427so

Opitz B, Förster S, Hocke AC, Maass M, Schmeck B, Hippenstiel S, Suttorp N, Krüll M. Nod1 mediated endothelial cell activation by C. pneumoniae. Circ. Res. 2005;96:319-26. https://doi.org/10.1161/01.res.0000155721.83594.2c

Mucosal surfaces of the upper respiratory tract and gut are physiologically colonized with their own collection of microbes, the microbiota. The normal upper respiratory tract and gut microbiota protects against lung infections by impeding colonization by potentially pathogenic bacteria and by regulating immune responses. Antimicrobial therapy and critical care procedures, however, can perturb the microbiota, thus compromising its function and predisposing to lung infections. We investigate how the healthy microbiota protects against lung infections and how host factors and medical interventions alter the microbiota, thus influencing susceptibility to pneumonia.

Project-related publications

Essex M*, Millet Pascual-Leone B*, Löber U, Kuhring M, Zhang B, Bruening U, Fritsche-Guenther R, Krzanowski M, Fiocca Vernengo F, Brumhard S, Röwekamp I, Anna Bielecka A, Till Lesker R, Wyler E, Landthaler M, Mantei A, Meisel C, Caesar S, Thibeault C, Corman V, Marko L, Suttorp N, Strowig T, Kurth F, Sander LE, Li Y, Kirwan JA*, Forslund SK*, Opitz B*. Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19. bioRxiv 2022.12.02.518860. https://doi.org/10.1101/2022.12.02.518860

Thibeault C, Suttorp N, Opitz B. The Microbiota in Pneumonia: From Protection to Predisposition. Science Transl. Med. 2021;13. https://doi.org/10.1126/scitranslmed.aba0501

Robak O, Heimesaat MM, Kruglov A, Prepens S, Gutbier B, Reppe K, Hochrein H, Suter M, Kirschning CJ, Schneider P, Witzenrath M, Bereswill S, Steinhoff U, Suttorp N, Sander LE, Chaput C*, Opitz B*. Antibiotic treatment-induced secondary IgA-deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia. J Clin Invest. 2018;28:3535-3545. https://doi.org/10.1172/jci97065

Maschirow L, Suttorp N, Opitz B. Microbiota-dependent regulation of antimicrobial immunity in the lung. Am J Respir Cell Mol Biol. 2019;61:284-289. https://doi.org/10.1165/rcmb.2019-0101tr

Various host factors (e.g. genetics, age), comorbidities (e.g. chronic and metabolic diseases), and medical interventions (e.g. critical care procedures, drug treatment) influence the risk for lung infections. We are investigating the underlying mechanisms and exploring targeted strategies to protect high-risk patients from pneumonia.

Project-related publications

Ruiz-Moreno JS, Hamann L, Shah JA, Verbon A, Mockenhaupt FP, Puzianowska-Kuznicka M, Naujoks J, Sander LE, Witzenrath M, Cambier JC, Suttorp N, Schumann RR, Jin L, Hawn TR, Opitz B, CAPNETZ Study Group. A common hypomorphic STING variant affects cGAS-dependent antibacterial defense and is associated with susceptibility to Legionnaires‘ disease in humans. PLOS Pathog. 2018;14:e1006829. https://doi.org/10.1371/journal.ppat.1006829