Madlen Hansen

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B6 Reprogramming of macrophages by the mycobacterial cord factor

Principal investigator
Roland Lang

Mentor
Anja Lührmann

Global and compartment-specific kinase activation in response to TDM via Mincle

Each year almost two million people die of tuberculosis. The pathogen, which is responsible for this fatal disease is the Mycobacterium tuberculosis, a Gram-positive and facultative intracellular bacterium. Based on specific survival mechanisms it is possible for Mycobacterium tuberculosis to survive and replicate in macrophages. For the prevention and treatment of tuberculosis it may be useful to understand the molecular mechanisms of these survival strategies. The glycolipid Trehalose-6,6-dimycolate (TDM) is a major constituent of the mycobacterial cell wall and was identified in the 1950s. This glycolipid is also known as cord factor and may play a dual role in infection. On the one hand TDM is a virulence factor of pathogenic mycobacteria, which inhibits the phagosome maturation. But on the other hand TDM is also recognized as a pathogen-associated molecular pattern (PAMP) that triggers the innate immune system. Our group and others have identified the CLR Mincle as the pattern recognition receptor for TDM and also for its synthetic analogue Trehalose-6,6-dibehenate (TDB). After TDM recognition, downstream signaling is effected by means of the Syk-Card9-Bcl10-Malt1 pathway.
In this work the effector functions and molecular mechanisms, triggered by the recognition of TDM via Mincle, shall be investigated more precisely to get more information about the reprogramming of macrophage signal transduction by the cord factor. For this we investigate the global and compartment-specific kinase activation in response to TDM via Mincle (Figure).

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Figure:Global [A] and compartment-specific [B] kinase activation in response to TDM via Mincle; A: recognition of TDM via Mincle and downstream signaling via the Syk-Card9-Bcl10-Malt1 pathway; B: Identification of adapter molecules, kinases and other signaling proteins recruited to the phagosome by proteome analysis.

 

Publications

 

 

Presentations

October 2016

8th Annual Retreat, Erlangen School of Molecular Communication, Schloss Schney, Lichtenfels, Germany
”The phosphoproteome of  Cord factor-activated macrophages”

Talk
     
March 2016

20th Minisymposium “Infection and Immunity”, Rothenfels Castle, Germany
”Modulation of kinase signaling in macrophages by Mincle activation”

Talk
     
November 2015

19th Joint Meeting “Signal Transduction – Receptors, Mediators and Genes”, STS, Weimar, Germany
”Modulation of kinase signaling in macrophages by Mincle activation”

Poster
     
October 2015

2nd International SFB796 Conference: Mechanisms of microbial host cell manipulation: From plants to humans, Erlangen, Germany
”Modulation of kinase signaling in macrophages by Mincle activation”

Poster
     
September 2015

67. Jahrestagung der Deutschen Gesellschaft für Hygiene und Mikrobiologie DGHM, Münster, Germany
”Modulation of kinase signaling in macrophages by Mincle activation”

Poster
     
July 2015 7th Annual Retreat, Erlangen School of Molecular Communication, Schloss Hirschberg, Beilngries, Germany
”Modulation of kinase signaling in macrophages by Mincle activation”
Poster
     
October 2014

66. Jahrestagung der Deutschen Gesellschaft für Hygiene und Mikrobiologie DGHM, Dresden, Deutschland
"Global and compartment-specific kinase activation in response to TDM via Mincle"

Poster
   
July 2014

6th Annual Retreat, Erlangen School of Molecular Communication, Kloster Banz, Bad Staffelstein, Germany
"Global and compartment-specific kinase activation in response to TDM via Mincle"

Poster