Du Bois, Ilona, Marsico, Annalisa, Bertrams, Wilhelm ORCID: 0000-0002-0180-2529, Schweiger, Michal R., Caffrey, Brian E., Sittka-Stark, Alexandra, Eberhardt, Martin, Vera, Julio ORCID: 0000-0002-3076-5122, Vingron, Martin and Schmeck, Bernd T. (2016). Genome-wide Chromatin Profiling of Legionella pneumophila-Infected Human Macrophages Reveals Activation of the Probacterial Host Factor TNFAIP2. J. Infect. Dis., 214 (3). S. 454 - 464. CARY: OXFORD UNIV PRESS INC. ISSN 1537-6613

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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 alpha-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-kappa B 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-kappa B-dependent factor relevant for bacterial replication.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Du Bois, IlonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marsico, AnnalisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bertrams, WilhelmUNSPECIFIEDorcid.org/0000-0002-0180-2529UNSPECIFIED
Schweiger, Michal R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caffrey, Brian E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sittka-Stark, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eberhardt, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vera, JulioUNSPECIFIEDorcid.org/0000-0002-3076-5122UNSPECIFIED
Vingron, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmeck, Bernd T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-267721
DOI: 10.1093/infdis/jiw171
Journal or Publication Title: J. Infect. Dis.
Volume: 214
Number: 3
Page Range: S. 454 - 464
Date: 2016
Publisher: OXFORD UNIV PRESS INC
Place of Publication: CARY
ISSN: 1537-6613
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LUNG EPITHELIUM; HISTONE MODIFICATIONS; CYTOKINE RELEASE; EXPRESSION; GENE; TRANSCRIPTION; CELLS; PNEUMONIAE; MICROARRAY; SEQUENCESMultiple languages
Immunology; Infectious Diseases; MicrobiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26772

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