Chlamydia pneumoniae Interferes with Macrophage Differentiation and Cell Cycle Regulation to Promote Its Replication

Show simple item record Taavitsainen-Wahlroos, Eveliina Miettinen, Ilkka Kortesoja, Maarit Reigada, Inés Savijoki, Kirsi Nyman, Tuula Anneli Hanski, Leena 2022-05-13T06:52:01Z 2022-05-13T06:52:01Z 2022-04-11
dc.identifier.citation Taavitsainen-Wahlroos , E , Miettinen , I , Kortesoja , M , Reigada , I , Savijoki , K , Nyman , T A & Hanski , L 2022 , ' Chlamydia pneumoniae Interferes with Macrophage Differentiation and Cell Cycle Regulation to Promote Its Replication ' , Cellular Microbiology , vol. 2022 , 9854449 .
dc.identifier.other PURE: 209238839
dc.identifier.other PURE UUID: 0e386813-9da1-49ec-bdf3-908338b2a828
dc.identifier.other ORCID: /0000-0002-3121-8542/work/113020370
dc.identifier.other ORCID: /0000-0002-1552-5956/work/113021659
dc.identifier.other ORCID: /0000-0003-1337-5998/work/113022638
dc.identifier.other WOS: 000791842900002
dc.description.abstract Chlamydia pneumoniae is a ubiquitous intracellular bacterium which infects humans via the respiratory route. The tendency of C. pneumoniae to persist in monocytes and macrophages is well known, but the underlying host-chlamydial interactions remain elusive. In this work, we have described changes in macrophage intracellular signaling pathways induced by C. pneumoniae infection. Label-free quantitative proteome analysis and pathway analysis tools were used to identify changes in human THP-1-derived macrophages upon C. pneumoniae CV6 infection. At 48-h postinfection, pathways associated to nuclear factor kappa B (NF-kappa B) regulation were stressed, while negative regulation on cell cycle control was prominent at both 48 h and 72 h. Upregulation of S100A8 and S100A9 calcium binding proteins, osteopontin, and purine nucleoside hydrolase, laccase domain containing protein 1 (LACC1) underlined the proinflammatory consequences of the infection, while elevated NF-kappa B2 levels in infected macrophages indicates interaction with the noncanonical NF-kappa B pathway. Infection-induced alteration of cell cycle control was obvious by the downregulation of mini chromosome maintenance (MCM) proteins MCM2-7, and the significance of host cell cycle regulation for C. pneumoniae replication was demonstrated by the ability of a cyclin-dependent kinase (CDK) 4/6 inhibitor Palbociclib to promote C. pneumoniae replication and infectious progeny production. The infection was found to suppress retinoblastoma expression in the macrophages in both protein and mRNA levels, and this change was reverted by treatment with a histone deacetylase inhibitor. The epigenetic suppression of retinoblastoma, along with upregulation of S100A8 and S100A9, indicate host cell changes associated with myeloid-derived suppressor cell (MDSC) phenotype. en
dc.format.extent 19
dc.language.iso eng
dc.relation.ispartof Cellular Microbiology
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 317 Pharmacy
dc.subject FACTOR-KAPPA-B
dc.subject IN-VITRO
dc.subject UP-REGULATION
dc.subject INFECTION
dc.subject GAMMA
dc.subject PROTEIN
dc.subject EXPRESSION
dc.subject RESPONSES
dc.title Chlamydia pneumoniae Interferes with Macrophage Differentiation and Cell Cycle Regulation to Promote Its Replication en
dc.type Article
dc.contributor.organization Faculty of Pharmacy
dc.contributor.organization Division of Pharmaceutical Biosciences
dc.contributor.organization Helsinki Institute of Sustainability Science (HELSUS)
dc.contributor.organization Explorations of Anti Infectives
dc.contributor.organization Pharmaceutical Design and Discovery group
dc.contributor.organization Department of Food and Nutrition
dc.contributor.organization The Academic Outreach Network
dc.contributor.organization Helsinki One Health (HOH)
dc.contributor.organization Divisions of Faculty of Pharmacy
dc.contributor.organization Drug Research Program
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1462-5814
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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