A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response.
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-λ 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-λ-mediated immune response to control bacterial colonization of the host.
Institut Pasteur, Unité des Interactions Bactéries Cellules, Paris, France.
Alice
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Lebreton
Goran
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Lakisic
Viviana
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Job
Lauriane
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Fritsch
To Nam
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Tham
Ana
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Camejo
Pierre-Jean
PJ
Matteï
Béatrice
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Regnault
Marie-Anne
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Nahori
Didier
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Cabanes
Alexis
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Gautreau
Slimane
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Ait-Si-Ali
Andréa
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Dessen
Pascale
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Cossart
Hélène
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Bierne
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D015398:Signal Transduction; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C543907:BAHD1 protein, human; C557013:BAHD1 protein, mouse; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D007378:Interleukins; D037521:Virulence Factors; D007372:Interferons