Počet záznamů: 1
Bordetella pertussis Adenylate Cyclase Toxin Blocks Induction of Bactericidal Nitric Oxide in Macrophages through cAMP-Dependent Activation of the SHP-1 Phosphatase
- 1.0451090 - MBÚ 2016 RIV US eng J - Článek v odborném periodiku
Černý, Ondřej - Kamanová, Jana - Mašín, Jiří - Bíbová, Ilona - Škopová, Karolína - Šebo, Peter
Bordetella pertussis Adenylate Cyclase Toxin Blocks Induction of Bactericidal Nitric Oxide in Macrophages through cAMP-Dependent Activation of the SHP-1 Phosphatase.
Journal of Immunology. Roč. 194, č. 10 (2015), s. 4901-4913. ISSN 0022-1767. E-ISSN 1550-6606
Grant CEP: GA ČR GAP302/12/0460; GA ČR GA13-14547S
Institucionální podpora: RVO:61388971
Klíčová slova: CYCLIC-AMP * MURINE MACROPHAGES * IFN-GAMMA
Kód oboru RIV: EE - Mikrobiologie, virologie
Impakt faktor: 4.985, rok: 2015
The adenylate cyclase toxin-hemolysin (CyaA) plays a key role in the virulence of Bordetella pertussis. CyaA penetrates complement receptor 3-expressing phagocytes and catalyzes uncontrolled conversion of cytosolic ATP to the key second messenger molecule cAMP. This paralyzes the capacity of neutrophils and macrophages to kill bacteria by complement-dependent oxidative burst and opsonophagocytic mechanisms. We show that cAMP signaling through the protein kinase A (PKA) pathway activates Src homology domain 2 containing protein tyrosine phosphatase (SHP) 1 and suppresses production of bactericidal NO in macrophage cells. Selective activation of PKA by the cell-permeable analog N-6-benzoyladenosine-3',5'-cyclic monophosphate interfered with LPS-induced inducible NO synthase (iNOS) expression in RAW264.7 macrophages, whereas inhibition of PKA by H-89 largely restored the production of iNOS in CyaA-treated murine macrophages. CyaA/cAMP signaling induced SHP phosphatase-dependent dephosphorylation of the c-Fos subunit of the transcription factor AP-1 and thereby inhibited TLR4-triggered induction of iNOS gene expression. Selective small interfering RNA knockdown of SHP-1, but not of the SHP-2 phosphatase, rescued production of TLR-inducible NO in toxin-treated cells. Finally, inhibition of SHP phosphatase activity by NSC87877 abrogated B. pertussis survival inside murine macrophages. These results reveal that an as yet unknown cAMP-activated signaling pathway controls SHP-1 phosphatase activity and may regulate numerous receptor signaling pathways in leukocytes. Hijacking of SHP-1 by CyaA action then enables B. pertussis to evade NO-mediated killing in sentinel cells of innate immunity.
Trvalý link: http://hdl.handle.net/11104/0252280
Název souboru Staženo Velikost Komentář Verze Přístup 125_Bordetella pertussis Adenylate Cyclase Toxin Blocks.pdf 5 1.4 MB Vydavatelský postprint vyžádat
Počet záznamů: 1