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Science 331 (6022): 1319-1321

Copyright © 2011 by the American Association for the Advancement of Science

A Bacterial Protein Targets the BAHD1 Chromatin Complex to Stimulate Type III Interferon Response

Alice Lebreton,1,2,3 Goran Lakisic,4 Viviana Job,5 Lauriane Fritsch,6 To Nam Tham,1,2,3 Ana Camejo,7 Pierre-Jean Matteï,5 Béatrice Regnault,8 Marie-Anne Nahori,1,2,3 Didier Cabanes,7 Alexis Gautreau,4 Slimane Ait-Si-Ali,6 Andréa Dessen,5 Pascale Cossart,1,2,3,* Hélène Bierne1,2,3,*

Abstract: Intracellular pathogens such as Listeria monocytogenes subvert cellular functions through the interaction of bacterial effectors with host components. Here we found that a secreted listerial virulence factor, LntA, could target the chromatin repressor BAHD1 in the host cell nucleus to activate interferon (IFN)–stimulated genes (ISGs). IFN-{lambda} expression was induced in response to infection of epithelial cells with bacteria lacking LntA; however, the BAHD1-chromatin associated complex repressed downstream ISGs. In contrast, in cells infected with lntA-expressing bacteria, LntA prevented BAHD1 recruitment to ISGs and stimulated their expression. Murine listeriosis decreased in BAHD1+/– mice or when lntA was constitutively expressed. Thus, the LntA-BAHD1 interplay may modulate IFN-{lambda}–mediated immune response to control bacterial colonization of the host.

1 Institut Pasteur, Unité des Interactions Bactéries Cellules, Paris F-75015, France.
2 Inserm, U604, Paris F-75015, France.
3 INRA, USC2020, Paris F-75015, France.
4 CNRS UPR3082, Laboratoire d’Enzymologie et de Biochimie Structurales, Gif-sur-Yvette F-91198, France.
5 Institut de Biologie Structurale, Bacterial Pathogenesis Group, UMR 5075 (CNRS/CEA/UJF), Grenoble F-38027, France.
6 CNRS UMR7216, Université Paris Diderot-Paris 7, Paris F-75013, France.
7 Institute for Molecular and Cellular Biology, Porto 4150, Portugal.
8 Institut Pasteur, Génopole, Paris F-75015, France.

* To whom correspondence should be addressed. E-mail: hbierne{at} (H.B.); pcossart{at} (P.C.)

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