Research Interests - Hélène Bierne

Ph.D. - INRA Research Director

helene.bierne@pasteur.fr
Pubmed bibliography

My research focuses on understanding how bacterial pathogens subvert host cell functions during infection to allow their survival, replication and resistance to immune responses. I specifically study how the pathogenic bacterium Listeria monocytogenes deregulates nuclear signaling pathways and exploits epigenetic mechanisms.

Our most recent work has identified the first bacterial factor targeting the host heterochromatin machinery (Lebreton et al., Science, 2011 Lebreton et al., Virulence, 2012). LntA secreted by intracellular Listeria counteracts repression by human BAHD1 to activate interferon responsive genes. We are also interested in other Listeria secreted proteins that may modulate nuclear processes (Personnic et al., Infect. Immun., 2011).


 

 

LntA is a nuclear protein

The BAHD1 chromatin-silencing complex

The BAHD1 chromatin-silencing complex

 

We have characterized the human protein BAHD1 as a novel chromatin regulator in vertebrates. BAHD1 acts as a silencer by tethering chromatin regulators (HP1, MBD1, KAP1) and chromatin-modifying enzymes (HMT and HDAC) to sequence-specific transcription factors, enabling local chromatin compaction at specific target genes. The set of genes repressed by the BAHD1 complex depends on the signal to which cells are submitted (Bierne et al. PNAS, 2009; Lebreton et al., Science, 2011).

Epigenetic, infection and immunity

Upon signaling induced by L. monocytogenes infection, the BAHD1 complex represses a set of immunity genes induced by type III interferons in epithelial cells. When bacteria secrete LntA, this factor prevents the action of BAHD1 and selectively activates interferon-responsive genes. Challenge of BAHD1+/- mice with Listeria highlights a role for BAHD1 in the negative regulation of host responses to bacterial infection.

We now address whether the Listeria-BAHD1 interplay leads to epigenetic modifications that play role in immune responses during infection. We are also investigating the role of type III interferons in bacterial infections (Bierne et al., Plos ONE, 2012).

Our future work aims to provide insights into epigenetic regulation of the immune system in health and disease.

Collaborators:

Alice Lebreton, Anupam Paliwal, Goran Lakisic.

Past collaborators:

Nicolas Personnic, Serawit Bruck, Christophe SabetAlix Rousseau.