Spring Selection 2020

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closes 25 October 2019

Research Groups

Portrait Alexander Dalpke

Alexander Dalpke

Infection & Immunity, Microbiome Studies

Previous and Current Research

My lab focuses on different aspects of infection & immunity. Currently three major topics are addressed:

Immunostimulation by nucleic acids

Cells of the innate immune system recognize conserved microbial structures, so called pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors. Among these receptors Toll-like receptors (TLR) 3, -7, -8, -9 and -13 recognize nucleic acids of viral, bacterial or synthetic origin. However, the exact mechanisms of nucleic acid recognition and the differentiation between foreign (dangerous) and self (usually harmless) are still only known partially. Work of our own could show that bacterial RNA represents a PAMP recognized by various immune cells. We could also show that former orphan TLR13 is a murine receptor for bacterial RNA. Posttranscriptional RNA modifications play a decisive role for self/non-self discrimination. Present work aims to further characterize the modes of bacterial RNA recognition and stimulation.

Immune functions of airway epithelium

We have shown that airway epithelial cells use TLRs for sensing infectious danger. However, TLRs are strictly regulated at mucosal surfaces to avoid overshooting reactions and to account for the specific needs of pathogen recognition in airways. We could show that bronchial epithelial cells regulate local dendritic cells and T-lymphocytes, thereby establishing a specific, tolerogenic microenvironment. We propose a concept of local immunity that is shaped by non-immune, stromal cells. We speculate that additional stressors are necessary to switch from a tolerogenic, homeostatic environment towards a reactive one upon true infection. ER stress was identified to be a kind of “second” signal that mediates this function. Recent work focuses on Pseudomonas aeruginosa and its immune-modulatory functions in Cystic Fibrosis.

Microbiome analysis in cystic fibrosis

Interactions between bacteria and their host represent a full continuum from pathogenicity to mutualism. From an evolutionary perspective, host-bacteria relationships are no longer considered a two-component ecological system but rather a complex interactive network. Cystic fibrosis (CF) is characterized by defective mucociliary clearance associated with polymicrobial chronic airway infections. Those infections, leading to persistent inflammation and periodic episodes of acute pulmonary exacerbation, contribute to an irreversible decline in CF lung function. We study CF lung microbiome aiming to answer different questions about CF microbiome resilience, antibiotic treatment effect and possible dysbiosis induced by exacerbation. Recent work focuses on interactions of commensal bacteria with Pseudomonas aeruginosa.

Alexander Dalpke Research: Figure
Figure: Recognition of bacterial RNA by different Toll-like receptors in innate immune cells and RNA modifications that inhibit activation
Future Projects and Goals

Future work aims to study the mechanisms of RNA recognition in physiological systems and to analyze whether and how the molecular mechanisms of nucleic acid self/foreign discrimination are disturbed in autoimmune diseases. Work in the lung project aims to decipher means by which airway epithelial cells can switch to an activation state and how this might affect chronic inflammatory airway diseases. In CF we try to translate findings from microbial ecology into new diagnostic procedures and treatment strategies.

Methodological and Technical Expertise
  • Magnetic cell sorting
  • In vivo infection models
  • Microbiome analysis pipeline
  • Precision cut lung slices
Selected Publications

Boutin S, Graeber SY, Stahl M, Dittrich SA, Mall MA and Dalpke AH
Chronic but not intermittent infection with Pseudomonas aeruginosa is associated with global changes of the lung microbiome in cystic fibrosis.
Eur Respir J 50 (4): 1701086 (2017)

Hidmark A, von Saint Paul A, Dalpke AH
Cutting Edge: TLR13 is a receptor for bacterial RNA.
J Immunol 189(6):2717–21 (2012)

Gehrig S, Eberle ME, Botschen F, Rimbach K, Eberle F, Eigenbrod T, Kaiser S, Holmes WM, Erdmann VA, Sprinzl M, Bec G, Keith G, Dalpke AH* and Helm M*
Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity.
J Exp Med 209 (2): 225–233 (2012) [*equal contribution]

Strebovsky J, Walker P, Lang R .and Dalpke AH
Suppressor of cytokine signaling 1 (SOCS1) limits NFκB signaling by decreasing p65 stability within the cell nucleus.
FASEB J. 25(3): 863–874 (2011)

Bätz A, Frey M, Heeg K and Dalpke AH
Suppressor of cytokine signaling (SOCS) proteins indi-rectly regulate Toll-like receptor signaling in innate immune cells.
J. Biol. Chem. 279(52), 54708–54715 (2004)

CV

Since 2019
Professor of Medical Microbiology; Director Institute of Med. Microbiology and Hygiene, Institute of Virology, Med. Faculty, Technical University Dresden

2011
Consultant in microbiology, virology and epidemiology of infections

2006–2018
Professor for Medical Microbiology and Infection and Immunity, Dept. of Medical Microbiology and Hygiene, University Heidelberg

2005–2006
Group Leader, Dept. of Medical Microbiology and Hygiene, University Heidelberg

2004
Habilitation, University lecturer for infection and immunity

1999–2004
Post-doc and Research Assistant, Inst. of Medical Microbiology, Philipps-University Marburg

1998–1999
First-year resident, Internal medicine

1998
Graduation (MD), Med. Microbiology, University Göttingen

Contact

Institute of Medical Microbiology and Hygiene
University Hospital Carl Gustav Carus
Technische Universität Dresden
Fetscherstraße 74
01307 Dresden, Germany

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