Developmental Biology & Disease Mechanisms | Genetics, Epigenetics & Gene Regulation | Immunology & Pathogens
Host responses and innate immunity to bacteria
The first line of defense against pathogenic microorganisms is set by the innate immune system which rapidly limits colonization and spread. To increase protection and produce immunological memory cells participating in the innate response initiate an adaptive immune response. Protection and immunoregulation by the innate immune system requires that a microbe is detected and physical contact is translated into altered gene expression of the infected cell...more
The first line of defense against pathogenic microorganisms is set by the innate immune system which rapidly limits colonization and spread. To increase protection and produce immunological memory cells participating in the innate response initiate an adaptive immune response. Protection and immunoregulation by the innate immune system requires that a microbe is detected and physical contact is translated into altered gene expression of the infected cell.
Antimicrobial gene products provide protective effector mechanisms. Moreover, secreted cytokines fulfill the task of communicating between cells involved in the antimicrobial response to maximize the common antimicrobial effort. One important group of cytokines is formed by the interferons (IFN), subdivided into three distinct classes (IFN-I, II, III). Collectively IFN play an indispensable role in the immune system both as regulators of antimicrobial cell activation and as modulators of the inflammation which accompanies infection.
Our research aims at understanding how the synthesis of IFN is initiated when cells or animals are infected with intracellular bacteria and how IFN give rise to changes in the cellular transcriptome. Microbial infection causes cellular signals that produce activated interferon regulatory factors (IRF), transcriptional regulators of the IFN genes. We have identified an RNA helicase, DDX3X, that enhances the ability of IRF to stimulate IFN transcription. Current activities aim at studying the importance of the DDX3X enzyme for innate immunity in cells and mice. Furthermore, we address the mechanism by which DDX3X contributes to transcriptional regulation of antimicrobial genes.
Once infected cells produce IFN these interact with cell surface receptors and set off cellular signals through Janus protein tyrosine kinases (JAKs) and transcription factors collectively called signal transducers and activators of transcription (STATs). A long-standing interest of the lab is how STATs influence the chromatin of target genes to support transcription. Related to this, we study the coordination of distinct signals in infected cells at chromatin level. Our particular interest is the transcriptional cooperativity of the JAK-STAT and NFκB pathways as a regulatory mechanism impacting on a large group of antimicrobial genes.
The overarching aim of our studies is to contribute to a comprehensive view of signaling and transcriptiome regulation in infected cells.close
Jamieson, Amanda M; Pasman, Lesley; Yu, Shuang; Gamradt, Pia; Homer, Robert J; Decker, Thomas; Medzhitov, Ruslan (2013). Role of Tissue Protection in Lethal Respiratory Viral-Bacterial Coinfection. SCIENCE. PMID: 23618765
Rauch, Isabella; Rosebrock, Felix; Hainzl, Eva; Heider, Susanne; Majoros, Andrea; Wienerroither, Sebastian; Strobl, Birgit; Stockinger, Silvia; Kenner, Lukas; Müller, Mathias; Decker, Thomas (2015). Noncanonical effects of IRF9 in intestinal inflammation: more than type I and type III interferons. MOL CELL BIOL;35(13):2332-43. PMID: 25918247
Wienerroither, Sebastian; Shukla, Priyank; Farlik, Matthias; Majoros, Andrea; Stych, Bernadette; Vogl, Claus; Cheon, HyeonJoo; Stark, George R; Strobl, Birgit; Müller, Mathias; Decker, Thomas (2015). Cooperative Transcriptional Activation of Antimicrobial Genes by STAT and NF-κB Pathways by Concerted Recruitment of the Mediator Complex. Cell Rep;12(2):300-12. PMID: 26146080
Special Research Program "Jak-Stat Signaling"
The Group Decker participates in the Special Research Area (SFB) "Jak-Stat Signaling: from Basics to Disease" funded by the Austrian Science Fund FWF. SFB's are peer-reviewed, highly interactive research networks, established to foster long-term, interdisciplinary co-operation of local research groups working on the frontiers of their thematic areas.