Systems Medicine of Community Acquired Pneumonia

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Aznaourova M, Janga H, Sefried S, Kaufmann A, Dorna J, Volkers SM, Georg P, Lechner M, Hoppe J, Dökel S, Schmerer N, Gruber AD, Linne U, Bauer S, Sander LE, Schmeck B, Schulte LN. Noncoding RNA MaIL1 is an integral component of the TLR4-TRIF pathway. Proc Natl Acad Sci U S A. 2020 Apr 21;117(16):9042-9053. doi: 10.1073/pnas.1920393117. Epub 2020 Apr 2.
Herkt CE, Caffrey BE, Surmann K, Blankenburg S, Gesell Salazar M, Jung AL, Herbel SM, Hoffmann K, Schulte LN, Chen W, Sittka-Stark A, Völker U, Vingron M, Marsico A, Bertrams W, Schmeck B. A MicroRNA Network Controls Legionella pneumophila Replication in Human Macrophages via LGALS8 and MX1. mBio. 2020 Mar 24;11(2). pii: e03155-19. doi: 10.1128/mBio.03155-19.
Hübner K, Karwelat D, Pietsch E, Beinborn I, Winterberg S, Bedenbender K, Benedikter BJ, Schmeck B, Vollmeister E. NF-κB-mediated inhibition of microRNA-149-5p regulates Chitinase-3-like 1 expression in human airway epithelial cells. Cell Signal. 2020 Mar;67:109498. doi:10.1016/j.cellsig.2019.109498. Epub 2019 Dec 16.
Müller-Redetzky H, Kellermann U, Wienhold SM, Gutbier B, Lienau J, Hellwig K, Reppe K, Letsiou E, Tschernig T, Scholz M, Ahnert P, Maasch C, Hoehlig K, Klussmann S, Vater A, Firsching TC, Hoppe J, Suttorp N, Witzenrath M. Neutralizing Complement C5a Protects Mice with Pneumococcal Pulmonary Sepsis. Anesthesiology. 2020 Feb 20. doi: 10.1097/ALN.0000000000003149.
Przybilla J, Ahnert P, Bogatsch H, Bloos F, Brunkhorst FM, SepNet Critical Care Trials Group, Progress Study Group, Bauer M, Loeffler M, Witzenrath M, Suttorp N, Scholz M. Markov State Modelling of Disease Courses and Mortality Risks of Patients with Community-Acquired Pneumonia. J Clin Med. 2020 Feb 5;9(2). pii: E393. doi: 10.3390/jcm9020393.
Bertrams W, Griss K, Han M, Seidel K, Klemmer A, Sittka-Stark A, Hippenstiel S, Suttorp N, Finkernagel F, Wilhelm J, Greulich T, Vogelmeier CF, Vera J, Schmeck B. Transcriptional analysis identifies potential biomarkers and molecular regulators in pneumonia and COPD exacerbation. Sci Rep. 2020 Jan 14;10(1):241. doi: 10.1038/s41598-019-57108-0.
Jung AL, Møller Jørgensen M, Bæk R, Griss K, Han M, Auf Dem Brinke K, Timmesfeld N, Bertrams W, Greulich T, Koczulla R, Hippenstiel S, Suttorp N, Schmeck B. Surface Proteome of Plasma Extracellular Vesicles as Biomarkers for Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease. J Infect Dis. 2020 Jan 2;221(2):325-335. doi: 10.1093/infdis/jiz460.
Lückel C, Picard F, Raifer H, Campos Carrascosa L, Guralnik A, Zhang Y, Klein M, Bittner S, Steffen F, Moos S, Marini F, Gloury R, Kurschus FC, Chao YY, Bertrams W, Sexl V, Schmeck B, Bonetti L, Grusdat M, Lohoff M, Zielinski CE, Zipp F, Kallies A, Brenner D, Berger M, Bopp T, Tackenberg B, Huber M. IL-17(+) CD8(+) T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis. Nat Commun. 2019 Dec 16;10(1):5722. doi: 10.1038/s41467-019-13731-z.
Lindhauer NS, Bertrams W, Pöppel A, Herkt CE, Wesener A, Hoffmann K, Greene B,Van Der Linden M, Vilcinskas A, Seidel K, Schmeck B. Antibacterial activity of a Tribolium castaneum defensin in an in vitro infection model of Streptococcuspneumoniae. Virulence. 2019 Dec;10(1):902-909.
Meyer TC, Schmidt F, Steinke J, Bröker BM, Völker U, Michalik S. Technical report: xMAPr - High-dynamic-range (HDR) quantification of antigen-specific antibody binding. J Proteomics. 2019 Nov 1:103577. doi: 10.1016/j.
Dabrowski AN, Shrivastav A, Conrad C, Komma K, Weigel M, Dietert K, Gruber AD,Bertrams W, Wilhelm J, Schmeck B, Reppe K, N'Guessan PD, Aly S, Suttorp N, HainT, Zahlten J. Peptidoglycan Recognition Protein 4 Limits Bacterial Clearance and Inflammation in Lungs by Control of the Gut Microbiota. Front Immunol. 2019 Sep20;10:2106. doi: 10.3389/fimmu.2019.02106. eCollection 2019.
Blankenburg S, Hentschker C, Nagel A, Hildebrandt P, Michalik S, Dittmar D, Surmann K, Völker U. Improving Proteome Coverage for Small Sample Amounts: An Advanced Method for Proteomics Approaches with Low Bacterial Cell Numbers. Proteomics. 2019 Sep 18:e1900192. doi: 10.1002/pmic.201900192.
Limburg H, Harbig A, Bestle D, Stein DA, Moulton HM, Jaeger J, Janga H, Hardes K, Koepke J, Schulte L, Koczulla AR, Schmeck B, Klenk HD, Böttcher-Friebertshäuser E. TMPRSS2 is the major activating protease of influenza A virus in primary human airway cells and influenza B virus in human type II pneumocytes. J Virol. 2019 Aug 7. pii: JVI.00649-19. doi: 10.1128/JVI.00649-19.
Brack MC, Lienau J, Kuebler WM, Witzenrath M. Cardiovascular sequelae of pneumonia. Curr Opin Pulm Med. 2019 May;25(3):257-262. doi: 10.1097/MCP.0000000000000584.
Wienhold SM, Lienau J, Witzenrath M. Towards Inhaled Phage Therapy in Western Europe. Viruses. 2019 Mar 23;11(3). pii: E295. doi: 10.3390/v11030295.
Kaplonek P, Khan N, Reppe K, Schumann B, Emmadi M, Lisboa MP, Xu FF, Calow ADJ, Parameswarappa SG, Witzenrath M, Pereira CL, Seeberger PH. Improving vaccines against Streptococcus pneumoniae using synthetic glycans. Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):13353-13358. doi: 10.1073/pnas.1811862115.
Berger S, Goekeri C, Gupta SK, Vera J, Dietert K, Behrendt U, Lienau J, Wienhold SM, Gruber AD, Suttorp N, Witzenrath M, Nouailles G. Delay in antibiotic therapy results in fatal disease outcome in murine pneumococcal pneumonia. Crit Care. 2018 Nov 1;22(1):287. doi: 10.1186/s13054-018-2224-5.
Wienhold SM, Macrì M, Nouailles G, Dietert K, Gurtner C, Gruber AD, Heimesaat MM, Lienau J, Schumacher F, Kleuser B, Opitz B, Suttorp N, Witzenrath M, Müller-Redetzky H. Ventilator-induced lung injury is aggravated by antibiotic mediated microbiota depletion in mice. Crit Care. 2018 Oct 29;22(1):282. doi: 10.1186/s13054-018-2213-8.
Marin-Sanguino A, Vera J, Alves R. Editorial: Foundations of Theoretical Approaches in Systems Biology. Front Genet. 2018 Aug 15;9:290. doi: 10.3389/fgene.2018.00290.
Vera J, Santos G. Can Gamification Contribute to Computer Modeling-Driven Biomedical Research? Front Physiol. 2018 Jul 19;9:908. doi: 10.3389/fphys.2018.00908. eCollection 2018.
Hopp L, Loeffler-Wirth H, Nersisyan L, Arakelyan A, Binder H. Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome. Front Immunol. 2018 Jul 17;9:1620. doi: 10.3389/fimmu.2018.01620
Gutbier B, Neuhauß AK, Reppe K, Ehrler C, Santel A, Kaufmann J, Scholz M, Weissmann N, Morawietz L, Mitchell TJ, Aliberti S, Hippenstiel S, Suttorp N, Witzenrath M; CAPNETZ and PROGRESS Study Groups ‡. Prognostic and Pathogenic Role of Angiopoietin-1 and -2 in Pneumonia. Am J Respir Crit Care Med. 2018 Jul 15;198(2):220-231. doi: 10.1164/rccm.201708-1733OC.
Santos G, Lai X, Eberhardt M, Vera J. Bacterial Adherence and Dwelling Probability: Two Drivers of Early Alveolar Infection by Streptococcus pneumoniae Identified in Multi-Level Mathematical Modeling. Front Cell Infect Microbiol. 2018 May 15;8:159. doi: 10.3389/fcimb.2018.00159. eCollection 2018.
Dietert K, Nouailles G, Gutbier B, Reppe K, Berger S, Jiang X, Schauer AE, Hocke AC, Herold S, Slevogt H, Witzenrath M, Suttorp N, Gruber AD. Digital Image Analyses on Whole-Lung Slides in Mouse Models of Acute Pneumonia. Am J Respir Cell Mol Biol. 2018 Apr;58(4):440-448. doi: 10.1165/rcmb.2017-0337MA.
Schumann B, Reppe K, Kaplonek P, Wahlbrink A, Anish C, Witzenrath M, Pereira CL, Seeberger PH. Development of an Efficacious, Semisynthetic Glycoconjugate Vaccine Candidate against Streptococcus pneumoniae Serotype 1. ACS Cent Sci. 2018 Mar 28;4(3):357-361. doi: 10.1021/acscentsci.7b00504.
Gutbier B, Schönrock SM, Ehrler C, Haberberger R, Dietert K, Gruber AD, Kummer W, Michalick L, Kuebler WM, Hocke AC, Szymanski K, Letsiou E, Lüth A, Schumacher F, Kleuser B, Mitchell TJ, Bertrams W, Schmeck B, Treue D, Klauschen F, Bauer TT, Tönnies M, Weissmann N, Hippenstiel S, Suttorp N, Witzenrath M; CAPNETZ Study Group. Sphingosine Kinase 1 Regulates Inflammation and Contributes to Acute Lung Injury in Pneumococcal Pneumonia via the Sphingosine-1-Phosphate Receptor 2. Crit Care Med. 2018 Mar;46(3):e258-e267. doi: 10.1097/CCM.0000000000002916.
Ruiz-Moreno JS, Hamann L, Jin L, Sander LE, Puzianowska-Kuznicka M, Cambier J, Witzenrath M, Schumann RR, Suttorp N, Opitz B. The cGAS/STING Pathway Detects Streptococcus pneumoniae but Appears Dispensable for Antipneumococcal Defense in Mice and Humans. Infect Immun. 2018 Feb 20;86(3). pii: e00849-17. doi: 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. The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires' disease in humans. PLoS Pathog. 2018 Jan 3;14(1):e1006829. doi: 10.1371/journal.ppat.1006829.
Jensen AV, Faurholt-Jepsen D, Egelund GB, Andersen SB, Petersen PT, Benfield T, Witzenrath M, Rohde G, Ravn P; German Community-Acquired Pneumonia Competence Network (CAPNETZ); German Community-Acquired Pneumonia Competence Network (CAPNETZ). Undiagnosed Diabetes Mellitus in Community-Acquired Pneumonia: A Prospective Cohort Study. Clin Infect Dis. 2017 Nov 29;65(12):2091-2098. doi: 10.1093/cid/cix703.
Gutbier B, Jiang X, Dietert K, Ehrler C, Lienau J, Van Slyke P, Kim H, Hoang VC, Maynes JT, Dumont DJ, Gruber AD, Weissmann N, Mitchell TJ, Suttorp N, Witzenrath M. Vasculotide reduces pulmonary hyperpermeability in experimental pneumococcal pneumonia. Crit Care. 2017 Nov 13;21(1):274. doi: 10.1186/s13054-017-1851-6.
Seeberger PH, Pereira CL, Khan N, Xiao G, Diago-Navarro E, Reppe K, Opitz B, Fries BC, Witzenrath M. A Semi-Synthetic Glycoconjugate Vaccine Candidate for Carbapenem-Resistant Klebsiella pneumoniae. Angew Chem Int Ed Engl. 2017 Nov 6;56(45):13973-13978. doi: 10.1002/anie.201700964.
Arakelyan A, Nersisyan L, Poghosyan D, Khondkaryan L, Hakobyan A, Löffler-Wirth H, Melanitou E, Binder H. Autoimmunity and autoinflammation: A systems view on signaling pathway dysregulation profiles. PLoS One. 2017 Nov 3;12(11):e0187572. doi: 10.1371/journal.pone.0187572.
Emmadi M, Khan N, Lykke L, Reppe K, G Parameswarappa S, Lisboa MP, Wienhold SM, Witzenrath M, Pereira CL, Seeberger PH. A Streptococcus pneumoniae Type 2 Oligosaccharide Glycoconjugate Elicits Opsonic Antibodies and Is Protective in an Animal Model of Invasive Pneumococcal Disease. J Am Chem Soc. 2017 Oct 18;139(41):14783-14791. doi: 10.1021/jacs.7b07836.
Lisboa MP, Khan N, Martin C, Xu FF, Reppe K, Geissner A, Govindan S, Witzenrath M, Pereira CL, Seeberger PH. Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5. Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11063-11068. doi: 10.1073/pnas.1706875114.
Schulz C, Lai X, Bertrams W, Jung AL, Sittka-Stark A, Herkt CE, Janga H, Zscheppang K, Stielow C, Schulte L, Hippenstiel S, Vera J, Schmeck B. THP-1-derived macrophages render lung epithelial cells hypo-responsive to Legionella pneumophila - a systems biology study. Sci Rep. 2017 Sep 20;7(1):11988. doi: 10.1038/s41598-017-12154-4.
Cantone M, Santos G, Wentker P, Lai X, Vera J. Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection. Front Physiol. 2017 Aug 30;8:645. doi: 10.3389/fphys.2017.00645
Jung AL, Herkt CE, Schulz C, Bolte K, Seidel K, Scheller N, Sittka-Stark A, Bertrams W, Schmeck B. Legionella pneumophila infection activates bystander cells differentially by bacterial and host cell vesicles. Sci Rep. 2017 Jul 24;7(1):6301. doi: 10.1038/s41598-017-06443-1.
Jentho E, Bodden M, Schulz C, Jung AL, Seidel K, Schmeck B, Bertrams W. microRNA-125a-3p is regulated by MyD88 in Legionella pneumophila infection andtargets NTAN1. PLoS One. 2017 Apr 26;12(4):e0176204. doi:10.1371/journal.pone.0176204
Schumann, B., Hahm, H.S., Parameswarappa, S.G., Reppe, K., Wahlbrink, A., Govindan, S., Kaplonek, P., Pirofski, L.-A., Witzenrath, M., Anish, C., Pereira, C.L., Seeberger, P.H., 2017. A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine. Sci Transl Med. 2017 Mar 8;9(380). pii: eaaf5347. doi: 10.1126/scitranslmed.aaf5347.
Wentker P, Eberhardt M, Dreyer FS, Bertrams W, Cantone M, Griss K, Schmeck B, Vera J. An Interactive Macrophage Signal Transduction Map Facilitates Comparative Analyses of High-Throughput Data. J Immunol. 2017 Mar 1;198(5):2191-2201. doi: 10.4049/jimmunol.1502513.
Jung, A.L., Hoffmann, K., Herkt, C.E., Schulz, C., Bertrams, W., Schmeck, B., 2017. Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages. J Vis Exp. 2017 Feb 22;(120). doi: 10.3791/55146.
Lienau, J., Müller-Redetzky, H., Suttorp, N., Witzenrath, M., 2016. [New Pathogenetic Concepts and Pharmacological Studies on Adjuvant Therapy in Severe Pneumonia]. Pneumologie 70, 372-378.
Garn, H., Bahn, S., Baune, B.T., Binder, E.B., Bisgaard, H., Chatila, T.A., Chavakis, T., Culmsee, C., Dannlowski, U., Gay, S., Gern, J., Haahtela, T., Kircher, T., Müller-Ladner, U., Neurath, M.F., Preissner, K.T., Reinhardt, C., Rook, G., Russell, S., Schmeck, B., Stappenbeck, T., Steinhoff, U., van Os, J., Weiss, S., Zemlin, M., Renz, H., 2016. Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation. J. Allergy Clin. Immunol. 138, 47-56.
Parameswarappa SG, Reppe K, Geissner A, Ménová P, Govindan S, Calow AD, Wahlbrink A, Weishaupt MW, Monnanda BP, Bell RL, Pirofski LA, Suttorp N, Sander LE, Witzenrath M, Pereira CL, Anish C, Seeberger PH. A Semi-synthetic Oligosaccharide Conjugate Vaccine Candidate Confers Protection against Streptococcus pneumoniae Serotype 3 Infection. Cell Chem Biol. 2016 Nov 17;23(11):1407-1416. doi: 10.1016/j.chembiol.2016.09.016
Kirschner F, Reppe K, Andresen N, Witzenrath M, Ebstein F, Kloetzel PM. Proteasome β5i Subunit Deficiency Affects Opsonin Synthesis and Aggravates Pneumococcal Pneumonia. PLoS One. 2016 Apr 21;11(4):e0153847. doi: 10.1371/journal.pone.0153847
Lai X, Wolkenhauer O, Vera J. Understanding microRNA-mediated gene regulatory networks through mathematical modelling. Nucleic Acids Res. 2016 Jul 27;44(13):6019-35. doi: 10.1093/nar/gkw550
Du Bois I, Marsico A, Bertrams W, Schweiger MR, Caffrey BE, Sittka-Stark A, Eberhardt M, Vera J, Vingron M, Schmeck BT. Genome-wide Chromatin Profiling of Legionella pneumophila-Infected Human Macrophages Reveals Activation of the Probacterial Host Factor TNFAIP2. J Infect Dis. 2016 Aug 1;214(3):454-63. doi: 10.1093/infdis/jiw171
Schirm S, Ahnert P, Wienhold S, Mueller-Redetzky H, Nouailles-Kursar G, Loeffler M, Witzenrath M, Scholz M. A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice. PLoS One. 2016 May 19;11(5):e0156047. doi: 10.1371/journal.pone.0156047
Arakelyan A, Nersisyan L, Petrek M, Löffler-Wirth H, Binder H. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases. Front Genet. 2016 May 6;7:79. doi: 10.3389/fgene.2016.00079
Griss K, Bertrams W, Sittka-Stark A, Seidel K, Stielow C, Hippenstiel S, Suttorp N, Eberhardt M, Wilhelm J, Vera J, Schmeck B. MicroRNAs Constitute a Negative Feedback Loop in Streptococcus pneumoniae-Induced Macrophage Activation. J Infect Dis. 2016 Jul 15;214(2):288-99. doi: 10.1093/infdis/jiw109
Jung AL, Stoiber C, Herkt CE, Schulz C, Bertrams W, Schmeck B. Legionella pneumophila-Derived Outer Membrane Vesicles Promote Bacterial Replication in Macrophages. PLoS Pathog. 2016 Apr 22;12(4)
Santos G, Nikolov S, Lai X, Eberhardt M, Dreyer FS, Paul S, Schuler G, Vera J. Model-based genotype-phenotype mapping used to investigate gene signatures of immune sensitivity and resistance in melanoma micrometastasis. Sci Rep. 2016 Apr 26;6:24967
Eberhardt M, Lai X, Tomar N, Gupta S, Schmeck B, Steinkasserer A, Schuler G, Vera J. Third-Kind Encounters in Biomedicine: Immunology Meets Mathematics and Informatics to Become Quantitative and Predictive. Methods Mol Biol. 2016;1386:135-79. doi: 10.1007/978-1-4939-3283-2_9
Schmeck B, Bertrams W, Lai X, Vera J. Systems Medicine for Lung Diseases: Phenotypes and Precision Medicine in Cancer, Infection, and Allergy. Methods Mol Biol. 2016;1386:119-33. doi: 10.1007/978-1-4939-3283-2_8
Reppe K, Radünzel P, Dietert K, Tschernig T, Wolff T, Hammerschmidt S, Gruber AD, Suttorp N, Witzenrath M. Pulmonary immunostimulation with MALP-2 in influenza virus-infected mice increases survival after pneumococcal superinfection. Infect Immun. 2015;83(12):4617-29
Müller-Redetzky H, Lienau J, Suttorp N, Witzenrath M. Therapeutic strategies in pneumonia: going beyond antibiotics. Eur Respir Rev. 2015;24(137):516-24
Witzenrath M. Endothelial progenitor cells for acute respiratory distress syndrome treatment: support your local sheriff! Am J Respir Crit Care Med. 2014 Jun 15;189(12):1452-5