cAMP signaling of Bordetella adenylate cyclase toxin blocks M-CSF triggered upregulation of iron acquisition receptors on differentiating CD14+ monocytes.

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F24%3A00588165" target="_blank" >RIV/61388971:_____/24:00588165 - isvavai.cz</a>

Výsledek na webu

<a href="https://journals.asm.org/doi/10.1128/msphere.00407-24" target="_blank" >https://journals.asm.org/doi/10.1128/msphere.00407-24</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1128/msphere.00407-24" target="_blank" >10.1128/msphere.00407-24</a>

Jazyk výsledku

angličtina

Název v původním jazyce

cAMP signaling of Bordetella adenylate cyclase toxin blocks M-CSF triggered upregulation of iron acquisition receptors on differentiating CD14+ monocytes.

Popis výsledku v původním jazyce

Bordetella pertussis infects the upper airways of humans and disarms host defense by the potent immuno-subversive activities of its pertussis (PT) and adenylate cyclase (CyaA) toxins. CyaA action near-instantly ablates the bactericidal activities of sentinel CR3-expressing myeloid phagocytes by hijacking cellular signaling pathways through the unregulated production of cAMP. Moreover, CyaA-elicited cAMP signaling also inhibits the macrophage colony-stimulating factor (M-CSF)-induced differentiationdifferentiationdifferentiationof incoming inflammatory monocytes into bactericidal macrophages. We show that CyaA/cAMP signaling via protein kinase A (PKA) downregulates the M-CSF-elicited expression of monocyte receptors for transferrin (CD71) and hemoglobin-haptoglobin (CD163), as well as the expression of heme oxygenase-1 (HO-1) involved in iron liberation from internalized heme. The impact of CyaA action on CD71 and CD163 levels in differentiating monocytes is largely alleviated by the histone deacetylase inhibitor trichostatin A (TSA), indicating that CyaA/cAMP signaling triggers epigenetic silencing of genes for micronutrient acquisition receptors. These results suggest a new mechanism by which B. pertussis evades host sentinel phagocytes to achieve proliferation on airway mucosa.

Název v anglickém jazyce

cAMP signaling of Bordetella adenylate cyclase toxin blocks M-CSF triggered upregulation of iron acquisition receptors on differentiating CD14+ monocytes.

Popis výsledku anglicky

Bordetella pertussis infects the upper airways of humans and disarms host defense by the potent immuno-subversive activities of its pertussis (PT) and adenylate cyclase (CyaA) toxins. CyaA action near-instantly ablates the bactericidal activities of sentinel CR3-expressing myeloid phagocytes by hijacking cellular signaling pathways through the unregulated production of cAMP. Moreover, CyaA-elicited cAMP signaling also inhibits the macrophage colony-stimulating factor (M-CSF)-induced differentiationdifferentiationdifferentiationof incoming inflammatory monocytes into bactericidal macrophages. We show that CyaA/cAMP signaling via protein kinase A (PKA) downregulates the M-CSF-elicited expression of monocyte receptors for transferrin (CD71) and hemoglobin-haptoglobin (CD163), as well as the expression of heme oxygenase-1 (HO-1) involved in iron liberation from internalized heme. The impact of CyaA action on CD71 and CD163 levels in differentiating monocytes is largely alleviated by the histone deacetylase inhibitor trichostatin A (TSA), indicating that CyaA/cAMP signaling triggers epigenetic silencing of genes for micronutrient acquisition receptors. These results suggest a new mechanism by which B. pertussis evades host sentinel phagocytes to achieve proliferation on airway mucosa.

Druh

J_ost - Ostatní články v recenzovaných periodicích

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

mSphere

ISSN

2379-5042

e-ISSN

2379-5042

Svazek periodika

9

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

00407-24

Kód UT WoS článku

001280622000001

EID výsledku v databázi Scopus

2-s2.0-85202790471