| Autor: |
Eveliina Taavitsainen-Wahlroos, Ilkka Miettinen, Maarit Ylätalo, Inés Reigada, Kirsi Savijoki, Tuula Anneli Nyman, Leena Hanski |
| Přispěvatelé: |
Faculty of Pharmacy, Division of Pharmaceutical Biosciences, Helsinki Institute of Sustainability Science (HELSUS), Explorations of Anti Infectives, Pharmaceutical Design and Discovery group, Department of Food and Nutrition, The Academic Outreach Network, Helsinki One Health (HOH), Divisions of Faculty of Pharmacy, Drug Research Program, Anti-infectives research |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cellular Microbiology. |
| ISSN: |
1462-5814 |
| DOI: |
10.1155/2022/9854449 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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