DAMP-induced proinflammatory feedback mechanisms between phagocytes and endothelial / epithelial barriers in infectious diseases

    Pulmonary infectious diseases are often amplified by mechanisms induced by endogenous ligands (DAMPs). The interplay of DAMPs and PAMPs lead to the breakdown of endothelial and epithelial lung barriers and overwhelming immune responses causing severe complications in clinical practice. Goal of the follow-up research project B08 is to further elucidate the S100A8/A9-TLR4/MD2-DAMP mechanism and the implications for the lung epithelial barrier for the development of new therapeutic options against pulmonary diseases. 

    Research area: Phagocyte biology, danger signalling

    Prof. Dr. rer. nat. Thomas Vogl

    Funding period: July 2012 - June 2020

    • Publications

      Original articles

      • Dreschers S, Ohl K, Lehrke M, Möllmann J, Denecke B, Costa I, Vogl T, Viemann D, Roth J, Orlikowsky T, Tenbrock K. (2019) Impaired cellular energy metabolism in cord blood macrophages contributes to abortive response toward inflammatory threats. Nat Commun 10:1685.
      • Helfen A, Große Hokamp N, Geyer C, Heindel W, Bremer C, Vogl T, Höltke C, Masthoff M, Barczyk-Kahlert K, Roth J, Wildgruber M, Eisenblaetter M. (2019) Target-Specific Imaging of Cathepsin and S100A8/A9 Reflects Specific Features of Malignancy and Enables Estimation of Tumor Malignancy. Mol Imaging Biol 2019 May 16. doi: 10.1007/s11307-019-01370-1.
      • Völler T, Faust A, Roth J, Schäfers M, Vogl T, Hermann S (2018) A non-peptidic S100A9 specific ligand for optical imaging of phagocyte activity in vivo, Mol Imaging Biol 20(3):407-416.
      • Vogl T, Stratis A, Wixler V, VöllerT, 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, Koenig S, Pap T & Roth J (2018) Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation, J. Clin. Invest. pii: 89867. (doi: 10.1172/JCI89867)   .
      • 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, Leandersson T, Schultze JL, König S, Pap T, Roth J. (2018) Auto-inhibitory regulation of S100A8/A9-alarmin activity locally restricts sterile inflammation. J Clin Invest 128:1852-1866.
      • Chakraborty D, Zenker S, Rossaint J, Hölscher A, Pohlen M, Zarbock A, Roth J and Vogl T (2017) Alarmin S100A8 Activates Alveolar Epithelial Cells in the Context of Acute Lung Injury in a TLR4-Dependent Manner. Front. Immunol. 8:1493. (doi: 10.3389/fimmu.2017.01493)
      • Dantas RL, Brachvogel B, Schied T, Bergmeier V, Skryabin B, Vogl T, Ludwig S & Wixler V (2017) The LIM-Only Protein Fhl2 Attenuates Development of Psoriatic Arthritis by Blocking Adam17-Mediated TNF Release. Am. J. Pathol. 187, 2388-2398. (doi: 10.1016/j.ajpath.2017.07. 015)
      • Eisenblätter M, Flores-Borja F, Lee JJ, Wefers C, Smith H, Hueting R, Cooper MS, Blower PJ, Patel D, Rodriguez-Justo M, Milewicz H, Vogl T, Roth J, Tutt A, Schaeffter T & Ng T (2017) Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment. Theranostics 7, 2392-2401. (doi: 10.7150/thno.17138)
      • Pirr S, Richter M, Fehlhaber B, Pagel J, Härtel C, Roth J, Vogl T and Viemann D (2017) High Amounts of S100-Alarmins Confer Antimicrobial Activity on Human Breast Milk Targeting Pathogens Relevant in Neonatal Sepsis. Front. Immunol. 8:1822. (doi: 10.3389/fimmu.2017.01822)
      • Spiekermann C, Russo A, Stenner M, Rudack C, Roth J & Vogl T (2017) Increased levels of S100A8/A9 in patients with peritonsillar abscess – a new promising diagnostic marker to differentiate between peritonsillar abscess and peritonsillitis. Dis. Markers 2017:9126560. (doi: 10.1155/2017/9126560)
      • Thölking G, Schuette-Nuetgen K, Vogl T, Dobrindt U, Kahl BC, Brand M, et al. (2017) Male kidney allograft recipients at risk for urinary tract infection? PLoS ONE 12(11): e0188262. (doi.org/10.1371/journal.pone.0188262)
      • Ulas T, Pirr S, Fehlhaber B, Bickes M, 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 (2017) S100-induced innate immune programming protects newborn infants from sepsis. Nat Immunol. 18, 622-632. (doi: 10.1038/ni.3745)
      • Dantas R, Masemann D, Schied T, Bergmeier V, Vogl T, Loser K, Brachvogel B, Varga G, Ludwig S & Wixler V (2016) Macrophage-mediated psoriasis can be suppressed by regulatory T lymphocytes. J Pathol. 240, 366-377. (doi: 10.1002/path.4786)
      • Heinemann AS, Pirr S, Fehlhaber B, Mellinger L, Burgmann J, Busse M, Ginzel M, Friesenhagen J, von Köckritz-Blickwede M, Ulas T, von Kaisenberg CS, Roth J, Vogl T & Viemann D (2016) In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock. FASEB J. 31, 1153-1164. (doi: 10.1096/fj.201601083R)
      • Wales P, Schuberth CE, Aufschnaiter R, Fels J, García-Aguilar I, Janning A, Dlugos CP, Schäfer-Herte M, Klingner C, Wälte M, Kuhlmann J, Menis E, Hockaday KL, Maier KC, Hou W, Russo A, Higgs HN, Pavenstädt H, Vogl T, Roth J, Qualmann B, Kessels MM, Martin DE, Mulder B & Wedlich-Söldner R (2016) Calcium-mediated actin reset (CaAR) mediates acute cell adaptations. Elife Dec 6;5. pii: e19850. (doi: 10.7554/eLife.19850)
      • Becker A, Große Hokamp N, Zenker S, Flores-Borja F, Barzcyk K, Varga G, Roth J, Geyer C, Heindel W, Bremer C, Vogl T*, Eisenblaetter M* (2015) In vivo visualisation of the alarmin S100A9 in tumor lesions allows for estimation of the individual malignant potential by evaluation of tumor host-cell interaction. J. Nuc. Med. 56:450-456. *Shared first or senior authorship
      • Fassl SK, Austermann J, Papantonopoulou O, Riemenschneider M, Xue J, Bertheloot D, Freise N, Spiekermann C, Witten A, Viemann D, Kirschnek S, Stoll M, Latz E, Schultze JL, Roth J, Vogl T (2015) Transcriptome assessment reveals a dominant role for TLR4 in the activation of human phagocytes by the alarmin MRP8. J. Immunol. 194:575-583.
      • Pruenster M, Kurz ARM, Chung KJ, Cao-Ehlker X, Bieber S, Nussbaum CF, Bierschenk S, Eggersmann TK, Rohwedder I, Heinig K, Immler R, Moser M, Koedel U, Gran S, McEver RP, Vestweber D, Verschoor A, Leandersson T, Chavakis T, Roth J, Vogl T,* Sperandio M* (2015) Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion. Nat Commun. 6:6915.
      • Van Crombruggen K, Vogl T, Pérez-Novo C, Holtappels G, Bachert C (2015) Differential release and deposition of S100A8/A9 proteins in inflamed upper airway tissue. Eur Respir J, in press [Oct 22. pii: ERJ-00159-2015. doi:10.1183/13993003.00159-2015].
      • Wache C, Klein M, Ostergaard C, Angele B, Häcker H, Pfister HW, Pruenster M, Sperandio M, Leanderson T, Roth J, Vogl T, Koedel U (2015) Myeloid-related protein 14 promote inflammation and injury in meningitis. J Infect Dis (in press).  (pii: jiv028. Epub ahead of print)
      • Austermann J, Friesenhagen J, Fassl SK, Ortkras T, Burgmann J, Barczyk-Kahlert K, Faist E, Zedler S, Pirr S, Rohde C, Müller-Tidow C, von Köckritz-Blickwede M, von Kaisenberg CS, Flohé SB, Ulas T, Schultze JL, Roth J, Vogl T, Viemann D (2014) Alarmins MRP8 and MRP14 Induce Stress Tolerance in Phagocytes under Sterile Inflammatory Conditions.Cell Rep 9(6): 2112-2123. (doi: 10.1016/j.celrep.2014.11.020. Epub 2014 Dec 11)
      • Vogl T, Eisenblätter M, Völler T, Zenker S, Hermann S, van Lent P, Faust A, Geyer C, Petersen B, Roebrock K, Schäfers M, Bremer C, Roth J (2014) Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity. Nat Commun 5: 4593.
      • Petersen B, Wolf M, Austermann J, van Lent PLEM, Foell D, Ahlmann M, Kupas V, Loser K, Sorg C, Roth J, Vogl T (2013) The alarmin Mrp8/14 as regulator of the adaptive immune response during allergic contact dermatitis. EMBO J 32: 100-111. [IF: 9.82]
      • Foell D, Wittkowski H, Kessel C, Lüken A, Weinhage T, Varga G, Vogl T, Wirth T, Viemann D, Björk P, van Zoelen MAD, Gohar F, Srikrishna G, Kraft M, Roth J (2013) Pro-inflammatory S100A12 can activate human monocytes via Toll-like Receptor 4. Am J Respir Crit Care Med 187: 1324-1334. [IF: 11.04]
      • Kuipers MT*, Vogl T*, Aslami H, Jongsma G, van den Berg E, Vlaar APJ, Roelofs JJTH, Juffermans NP, Schultz MJ, van der Poll T, Roth J, Wieland CW (2013) High levels of S100A8/A9 proteins aggravate ventilator-induced lung injury via TLR4 signaling. PLoS One 8: e68694. [IF: 3.73] * Both authors made equal contributions.
      • Gopal R, Monin L, Torres D, Slight S, Mehra S, McKenna K, Fallert-Junecko BA, Reinhart TA, Kolls J, Báez-Saldaña R, Cruz-Lagunas A, Rodríguez-Reyna TS, Kumar NP, Tessier P, Roth J, Selman M, Becerril-Villanueva E, Baquera-Heredia J, Cumming B, Kasprowicz VO, Steyn AJ, Babu S, Kaushal D, Zúñiga J, Vogl T, Rangel-Moreno J, Khader SA (2013) S100A8/A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis. Am J Respir Crit Care Med 188: 1137-1146. [IF: 11.04]