Bordetella adenylate cyclase toxin elicits chromatin remodeling and transcriptional reprogramming that blocks differentiation of monocytes into macrophages
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F25%3A00619137" target="_blank" >RIV/61388971:_____/25:00619137 - isvavai.cz</a>
Result on the web
<a href="https://journals.asm.org/doi/epub/10.1128/mbio.00138-25" target="_blank" >https://journals.asm.org/doi/epub/10.1128/mbio.00138-25</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1128/mbio.00138-25" target="_blank" >10.1128/mbio.00138-25</a>
Alternative languages
Result language
angličtina
Original language name
Bordetella adenylate cyclase toxin elicits chromatin remodeling and transcriptional reprogramming that blocks differentiation of monocytes into macrophages
Original language description
Bordetella pertussis infects human upper airways and deploys an array of immunosuppressive virulence factors, among which the adenylate cyclase toxin (CyaA) plays a prominent role in disarming host phagocytes. CyaA binds the complement receptor-3 (CR3 aka alpha(M)beta(2) integrin CD11b/CD18 or Mac-1) of myeloid cells and delivers into their cytosol an adenylyl cyclase enzyme that hijacks cellular signaling through unregulated conversion of cytosolic ATP to cAMP. We found that the action of as little CyaA as 22 pM (4 ng/mL) blocks macrophage colony-stimulating factor (M-CSF)-driven transition of migratory human CD14(+) monocytes into macrophages. Global transcriptional profiling (RNAseq) revealed that exposure of monocytes to 22 pM CyaA for 40 hours in culture with 20 ng/mL of M-CSF led to upregulation of genes that exert negative control of monocyte to macrophage differentiation (e.g., SERPINB2, DLL1, and CSNK1E). The sustained CyaA action yielded downregulation of numerous genes involved in processes crucial for host defense, such as myeloid cell differentiation, chemotaxis of inflammatory cells, antigen presentation, phagocytosis, and bactericidal activities. CyaA-elicited signaling also promoted deacetylation and trimethylation of lysines 9 and 27 of histone 3 (H3K9me3 and H3K27me3) and triggered the formation of transcriptionally repressive heterochromatin patches in the nuclei of CyaA-exposed monocytes. These effects were partly reversed by the G9a methyltransferase inhibitor UNC 0631 and by the pleiotropic HDAC inhibitor Trichostatin-A, revealing that CyaA-elicited epigenetic alterations mediate transcriptional reprogramming of monocytes and play a role in CyaA-triggered block of monocyte differentiation into bactericidal macrophage cells.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10606 - Microbiology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
mBio
ISSN
2150-7511
e-ISSN
2150-7511
Volume of the periodical
16
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
21
Pages from-to
00138-25
UT code for WoS article
001447498500001
EID of the result in the Scopus database
2-s2.0-105002225175