Know more

About cookies

What is a "cookie"?

A "cookie" is a piece of information, usually small and identified by a name, which may be sent to your browser by a website you are visiting. Your web browser will store it for a period of time, and send it back to the web server each time you log on again.

Different types of cookies are placed on the sites:

  • Cookies strictly necessary for the proper functioning of the site
  • Cookies deposited by third party sites to improve the interactivity of the site, to collect statistics

Learn more about cookies and how they work

The different types of cookies used on this site

Cookies strictly necessary for the site to function

These cookies allow the main services of the site to function optimally. You can technically block them using your browser settings but your experience on the site may be degraded.

Furthermore, you have the possibility of opposing the use of audience measurement tracers strictly necessary for the functioning and current administration of the website in the cookie management window accessible via the link located in the footer of the site.

Technical cookies

Name of the cookie

Purpose

Shelf life

CAS and PHP session cookies

Login credentials, session security

Session

Tarteaucitron

Saving your cookie consent choices

12 months

Audience measurement cookies (AT Internet)

Name of the cookie

Purpose

Shelf life

atid

Trace the visitor's route in order to establish visit statistics.

13 months

atuserid

Store the anonymous ID of the visitor who starts the first time he visits the site

13 months

atidvisitor

Identify the numbers (unique identifiers of a site) seen by the visitor and store the visitor's identifiers.

13 months

About the AT Internet audience measurement tool :

AT Internet's audience measurement tool Analytics is deployed on this site in order to obtain information on visitors' navigation and to improve its use.

The French data protection authority (CNIL) has granted an exemption to AT Internet's Web Analytics cookie. This tool is thus exempt from the collection of the Internet user's consent with regard to the deposit of analytics cookies. However, you can refuse the deposit of these cookies via the cookie management panel.

Good to know:

  • The data collected are not cross-checked with other processing operations
  • The deposited cookie is only used to produce anonymous statistics
  • The cookie does not allow the user's navigation on other sites to be tracked.

Third party cookies to improve the interactivity of the site

This site relies on certain services provided by third parties which allow :

  • to offer interactive content;
  • improve usability and facilitate the sharing of content on social networks;
  • view videos and animated presentations directly on our website;
  • protect form entries from robots;
  • monitor the performance of the site.

These third parties will collect and use your browsing data for their own purposes.

How to accept or reject cookies

When you start browsing an eZpublish site, the appearance of the "cookies" banner allows you to accept or refuse all the cookies we use. This banner will be displayed as long as you have not made a choice, even if you are browsing on another page of the site.

You can change your choices at any time by clicking on the "Cookie Management" link.

You can manage these cookies in your browser. Here are the procedures to follow: Firefox; Chrome; Explorer; Safari; Opera

For more information about the cookies we use, you can contact INRAE's Data Protection Officer by email at cil-dpo@inrae.fr or by post at :

INRAE

24, chemin de Borde Rouge -Auzeville - CS52627 31326 Castanet Tolosan cedex - France

Last update: May 2021

Menu Logo Principal

Home page

Micalis

Epigenetics and Cellular Microbiology / Helene Bierne

EPIMIC

Helene et Ale

 

Team Leader and Co-Leader: Helene Bierne & Alessandro Pagliuso

RESEARCH AXIS AND ONGOING PROJECTS

The EPIMIC team focuses on the long-term impact of pathogenic bacteria on health. We study the molecular basis of persistent bacterial infections, as well as the epigenetic consequences of these infections on host cells. This research aims to find new ways of treatment against recurrent infections, and against bacterial imprints that may contribute to the genesis of chronic and complex diseases, such as cancer and autoimmune and metabolic diseases.

Our model is the facultative intracellular bacterium Listeria monocytogenes, which, like viruses, has developed highly sophisticated mechanisms to deregulate and exploit signaling pathways in mammalian cells. It is noteworthy that several of these signaling pathways are also involved in carcinogenesis and other adverse health effects. Thus, through the study of Listeria, we can highlight the function of human proteins, whose deregulation could lead to both infectious and other diseases.

Persistence and VBNC state of Listeria in intracellular vacuoles

liscv site web best

The pathogenicity of Listeria monocytogenes is related to its ability to invade different types of cells, including epithelial cells of the intestine, liver, brain and placenta. When it reaches the cytoplasm of these cells, L. monocytogenes proliferates and uses the force of actin polymerizationto move into the cytosol and spread to neighboring cells. This phase allows Listeria to disseminate in the tissues of the body. Using an in vitro experimental model of long-term infection in human epithelial cells, we have shown that after 2-3 days of infection in hepatocytes and placental cells, L. monocytogenes switches from the active cytosolic lifestyle to a quiescent vacuolar lifestyle. Bacteria cease to produce ActA (the protein that triggers actin polymerization at the bacterial surface), and cytosolic bacteria are engulfed in lysosomal vacuoles (Listeria-containing vacuoles, "LisCVs"). Subpopulations of vacuolar bacteria survive as slow/non-replicating forms, which retain the ability to reactivate as disseminating forms. In the absence of ActA, bacteria can even parasitize host cells in viable but non-culturable (VBNC) state, which renders Listeria undetectable on standard agar plates used in clinical microbiology (Kortebi et al. 2017). Host cells carrying Listeria VBNC may not be recognized and destroyed efficiently by immune cells. Related to this idea, we recently demonstrated that the vacuolar persistence phase in hepatocytes coincided with transcriptional inhibition of genes encoding acute phase proteins, which are important effectors of innate immunity (Descoeudres et al., 2021).

Figure 8_revised

These results reveal the ability of Listeria to generate intracellular persistent forms, which could be asymptomatically carried in humans or animals in the long-term (Bierne et al. 2018)(Lotoux et al. 2022).

Epigenetics, infection and immunity

Image-fusionnee

We found that Listeria targets the human protein BAHD1, which act as a transcriptional repressor by promoting heterochromatin formation (Bierne et al. 2009, Lebreton et al. 2011, Lebreton et al. 2014). Upon signaling induced by L. monocytogenes infection, the BAHD1 complex represses a set of immunity genes induced by interferons (particularly, Type III interferon or IFN lambda) in epithelial cells. When bacteria secrete the protein LntA, this factor prevents the action of BAHD1 in the nucleus and selectively activates interferon-stimulated genes (Lebreton et al., 2011). LntA interacts directly with a central proline-rich domain of BAHD1 via a surface patch of conserved positive charges. Two lysines within this patch are required for LntA function (Lebreton et al. 2014).    

These results have contributed to demonstrate that a pathogenic bacterium can fine-tune the expression of immunity genes by controling negatively or positively the function of epigenetics regulators (Bierne and Hamon 2020).

LntA is a paradigm for the emerging class of bacterial effectors entering the nucleus and hijacking nuclear processes, termed “nucleomodulins” (Bierne and Pourpre, 2020). Studying nucleomodulins can generate new insights into long-term impacts of infectious diseases. Our work now aims to characterize epimutations induced by these factors and by other bacterial stimuli, and to investigate whether these “patho-epimutations” reprogram host cells.

The epigenetic factor BAHD1

BAHD1 is a chromatin-bound factor that defines a novel histone deacetylase repressive complex involved in epigenetic regulation. BAHD1 acts by tethering chromatin regulators (MIER1, HP1, MBD1, KAP1) and chromatin-modifying enzymes (HMT and HDAC) to sequence-specific transcription factors, enabling local chromatin compaction (Bierne et al. 2009, Lebreton et al. 2011). In addition, BAHD1-mediated heterochromatin formation is linked to DNA methylation and may contribute to the spatial architecture of the genome (Libertini et al. 2015).

BAHD1 deficiency in mice results in defects in placental development and cholesterol homeostasis (Lakisic et al. 2016), as well as as anxiety-like phenotypes (Pourpre et al. 2020). Il also affects  bacterial infections (Lebreton et al. 2011).

BAHD1 site web2020

Publications (link to pubmed)

Fundings

This research has been supported by INRAE, the French National Research Agency (ANR), the Ligue de Recherche Contre le Cancer and the iXcore Research Fundation.