A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response

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

1 Equipe avenir - Microorganismes et Barrières de l'Hôte
2 UIBC - Interactions Bactéries-Cellules
3 LEBS - Laboratoire d'Enzymologie et Biochimie Structurales
4 IBS - UMR 5075 - Institut de biologie structurale
5 EDC (UMR_7216) - Centre épigénétique et destin cellulaire
6 IBMC - Instituto de Biologia Molecular e Celular
7 Génopole
8 INRAE - Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement

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.

Keywords: KAP1; Immunity; Listeria-Monocytogenes

Keywords: Infection; Lambda

Domains: Life Sciences [q-bio]; Cellular Biology; Subcellular Processes [q-bio.SC]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Molecular biology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Structural Biology [q-bio.BM]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Genomics [q-bio.GN]; Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology

Alice Lebreton, Goran Lakisic, Viviana Job, Lauriane Fritsch, To Nam Tham, et al.. A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response. Science, 2011, 331 (6022), pp.1319-21. ⟨10.1126/science.1200120⟩. ⟨cea-00819299⟩