Disease Area Coordinators

Prof. Dr. Susanne Herold (UGMLC), Prof. Dr. Tobias Welte (BREATH)

(Administr. Coordinator: Dr. Sylvia Weißmann (UGMLC))

Contributing Partner Sites

ARCN, BREATH, CPC-M, TLRC, UGMLC

OVERVIEW

Acute lower respiratory tract infections represent an increasing public health problem worldwide, resulting in a disease burden greater than that of any other infection with mortality rates unchanged over the past 50 years. Likewise, the lack of any pharmacological treatment for the most devastating clinical course of pulmonary infection, the acute respiratory distress syndrome (ARDS), coupled with an unacceptably high mortality rate, underscores an urgent medical need for novel, effective therapeutic approaches. The DZL aims to dissect the molecular mechanisms underlying the sensing of, and signaling in response to microbial insult and inflammatory infiltration with the aim of developing targeted interventions to attenuate lung injury in pneumonia and ARDS.

MAJOR RESEARCH GOALS

  • Genetic/epigenetic/transcriptomic/proteomic/miRNA signatures as biomarkers for individualized acute lung injury (ALI) treatment
  • Preclinical/clinical development of local-progenitor/stem cell-based ALI repair strategies
  • Novel protein-based immunization strategies and non-antibiotic targets for ALI prevention and treatment
  • Preclinical evaluation of targeted and spatially/temporally restricted interventions to attenuate lung injury preserving host defense and repair capacity
  • Cell-specific in-vivo and in-vitro dissection of lung immune responses during infection
  • Lung cell-specific role of pattern (microbes, damage) recognition receptors (PRR)

Pneumonia and Acute Lung Injury:  Selected Publications from DZL Faculty Members Published Since 2010

Hoegner K, Wolff T, Pleschka S, Plog S, Gruber AD, Kalinke U, Walmrath HD, Bodner J, Gattenlöhner S, Lewe-Schlosser P, Matrosovich M, Seeger W, Lohmeyer J, Herold S. Macrophage-expressed IFN-β Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia. PLoS One 2013; 9, e1003188.

Steinwede K, Henken S, Bohling J, Maus R, Ueberberg B, Brumshagen C, Brincks EL, Griffith TS, Welte T, Maus UA. TNF-related apoptosis-inducing ligand (TRAIL) exerts therapeutic efficacy for the treatment of pneumococcal pneumonia in mice.  Journal of Experimental Medicine 2013; 209 (11), pp. 1937-1952.

Brumshagen C, Maus R, Bischof A, Ueberberg B, Bohling J, Osterholzer JJ, Ogunniyi AD, Paton JC, Welte T, Maus UA.   FMS-like tyrosine kinase 3 ligand treatment of mice aggravates acute lung injury in response to Streptococcus pneumoniae: Role of pneumolysin. Infection and Immunity 2012; 80 (12), pp. 4281-4290.

Hackstein H, Hagel N, Knoche A, Kranz S, Lohmeyer J, von Wulffen W, Kershaw O, Gruber AD, Bein G, Baal N. Skin TLR7 triggering promotes accumulation of respiratory dendritic cells and natural killer cells. PLoS One 2012; 7, e43320.

Saffarzadeh M, Juenemann C, Queisser MA, Lochnit G, Barreto G, Galuska SP, Lohmeyer J, Preissner KT. Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS One 2012; 7:1-14 (e32366).

Unkel B, Hoegner K, Clausen BE, Lewe-Schlosser P, Bodner J, Gattenloehner S, Janßen H, Seeger W, Lohmeyer J, Herold S. Alveolar epithelial cells orchestrate DC function in murine viral pneumonia. J Clin Inv 2012;  122:3652-64.

Weber, M, Lambeck S, Ding N, Henken S, Kohl M, Deigner HP, Enot DP, Igwe EI, Frappart L, Kiehntopf M, Claus RA, Kamrad, T, Weih D, Vodovotz Y, Briles DE, Ogunniyi AD, Paton JC, Maus UA, Bauer M. Hepatic induction of cholesterol biosynthesis reflects a remote adaptive response to pneumococcal pneumonia.  FASEB Journal 2012; 26 (6) , pp. 2424-2436.

Hahn I, Klaus A, Janze AK, Steinwede K, Ding N, Bohling J, Brumshagen C, Serrano H, Gauthier F, Paton JC, Welte T, Maus UA. Cathepsin G and neutrophil elastase play critical and nonredundant roles in lung-protective immunity against Streptococcus pneumoniae in mice.  Infection and Immunity 2011; 79 (12) , pp. 4893-4901.

Herold S, Shafiei Tabar T, Janßen H, Högner, K, Cabanski M, Lewe-Schlosser P, Albrecht J, Driever F, Vadasz I, Seeger W, Steinmüller M, Lohmeyer J. Exudate macrophages attenuate epithelial injury by the release of IL-1 receptor antagonist in gram-negative pneumonia. Am J Respir Crit Care Med 2011; 183:1380-90 (IF 10.191).

Steinwede K, Tempelhof O, Bolte K, Maus R, Bohling J, Ueberberg B, Länger F, Christman JW, Paton JC, Ask K, Maharaj S, Kolb M, Gauldie J, Welte T, Maus UA. Local delivery of GM-CSF protects mice from lethal pneumococcal pneumonia.  Journal of Immunology 2011; 187 (10), pp. 5346-56.