Ilona Du Bois1, Annalisa Marsico2, Wilhelm Bertrams1, Michal R Schweiger3, Brian E Caffrey4, Alexandra Sittka-Stark1, Martin Eberhardt5, Julio Vera5, Martin Vingron4, Bernd T Schmeck6. 1. Institute for Lung Research/iLung Universities of Giessen and arburg Lung Centre, German Center for Lung Research. 2. Max Planck Institute for Molecular Genetics Free University, Berlin. 3. Functional Epigenomics, University of Cologne. 4. Max Planck Institute for Molecular Genetics. 5. Laboratory of Systems Tumor Immunology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, Germany. 6. Institute for Lung Research/iLung Department of Medicine, Pulmonary, and Critical Care Medicine, University Medical Center Marburg, Philipps-University Universities of Giessen and arburg Lung Centre, German Center for Lung Research.
Abstract
BACKGROUND: Legionella pneumophila is a causative agent of severe pneumonia. Infection leads to a broad host cell response, as evident, for example, on the transcriptional level. Chromatin modifications, which control gene expression, play a central role in the transcriptional response to L. pneumophila METHODS: We infected human-blood-derived macrophages (BDMs) with L. pneumophila and used chromatin immunoprecipitation followed by sequencing to screen for gene promoters with the activating histone 4 acetylation mark. RESULTS: We found the promoter of tumor necrosis factor α-induced protein 2 (TNFAIP2) to be acetylated at histone H4. This factor has not been characterized in the pathology of L. pneumophila TNFAIP2 messenger RNA and protein were upregulated in response to L. pneumophila infection of human-BDMs and human alveolar epithelial (A549) cells. We showed that L. pneumophila-induced TNFAIP2 expression is dependent on the NF-κB transcription factor. Importantly, knock down of TNFAIP2 led to reduced intracellular replication of L. pneumophila Corby in A549 cells. CONCLUSIONS: Taken together, genome-wide chromatin analysis of L. pneumophila-infected macrophages demonstrated induction of TNFAIP2, a NF-κB-dependent factor relevant for bacterial replication.
BACKGROUND: Legionella pneumophila is a causative agent of severe pneumonia. Infection leads to a broad host cell response, as evident, for example, on the transcriptional level. Chromatin modifications, which control gene expression, play a central role in the transcriptional response to L. pneumophila METHODS: We infected human-blood-derived macrophages (BDMs) with L. pneumophila and used chromatin immunoprecipitation followed by sequencing to screen for gene promoters with the activating histone 4 acetylation mark. RESULTS: We found the promoter of tumor necrosis factor α-induced protein 2 (TNFAIP2) to be acetylated at histone H4. This factor has not been characterized in the pathology of L. pneumophilaTNFAIP2 messenger RNA and protein were upregulated in response to L. pneumophila infection of human-BDMs and humanalveolar epithelial (A549) cells. We showed that L. pneumophila-induced TNFAIP2 expression is dependent on the NF-κB transcription factor. Importantly, knock down of TNFAIP2 led to reduced intracellular replication of L. pneumophila Corby in A549 cells. CONCLUSIONS: Taken together, genome-wide chromatin analysis of L. pneumophila-infected macrophages demonstrated induction of TNFAIP2, a NF-κB-dependent factor relevant for bacterial replication.
Authors: Annalisa Marsico; Wilhelm Bertrams; Bernd Schmeck; Christina E Herkt; Brian E Caffrey; Kristin Surmann; Sascha Blankenburg; Manuela Gesell Salazar; Anna L Jung; Stefanie M Herbel; Kerstin Hoffmann; Leon N Schulte; Wei Chen; Alexandra Sittka-Stark; Uwe Völker; Martin Vingron Journal: mBio Date: 2020-03-24 Impact factor: 7.867