Počet záznamů: 1
cAMP Signaling of Adenylate Cyclase Toxin Blocks the Oxidative Burst of Neutrophils through Epac-Mediated Inhibition of Phospholipase C Activity
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SYSNO ASEP 0473551 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název cAMP Signaling of Adenylate Cyclase Toxin Blocks the Oxidative Burst of Neutrophils through Epac-Mediated Inhibition of Phospholipase C Activity Tvůrce(i) Černý, Ondřej (MBU-M)
Anderson, K.E. (GB)
Stephens, L.R. (GB)
Hawkins, P.T. (GB)
Šebo, Peter (MBU-M) RID, ORCIDZdroj.dok. Journal of Immunology. - : American Association of Immunologists - ISSN 0022-1767
Roč. 198, č. 3 (2017), s. 1285-1296Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova BORDETELLA-PERTUSSIS ; NADPH OXIDASE ; CYCLIC-AMP Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Microbiology CEP GA13-14547S GA ČR - Grantová agentura ČR LM2015064 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora MBU-M - RVO:61388971 UT WOS 000392412700031 EID SCOPUS 85014714905 DOI 10.4049/jimmunol.1601309 Anotace The adenylate cyclase toxin-hemolysin (CyaA) plays a key role in immune evasion and virulence of the whooping cough agent Bordetella pertussis. CyaA penetrates the complement receptor 3 expressing phagocytes and ablates their bactericidal capacities by catalyzing unregulated conversion of cytosolic ATP to the key second messenger molecule cAMP. We show that signaling of CyaA-generated cAMP blocks the oxidative burst capacity of neutrophils by two converging mechanisms. One involves cAMP/ protein kinase A mediated activation of the Src homology region 2 domain containing phosphatase-1 (SHP-1) and limits the activation of MAPK ERK and p38 that are required for assembly of the NADPH oxidase complex. In parallel, activation of the exchange protein directly activated by cAMP (Epac) provokes inhibition of the phospholipase C by an as yet unknown mechanism. Indeed, selective activation of Epac by the cell-permeable analog 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate counteracted the direct activation of phospholipase C by 2,4,6-trimethyl-N43-(trifluoromethyl)phenylbenzenesulfonamide. Hence, by inhibiting production of the protein kinase C activating lipid, diacylglycerol, cAMP/Epac signaling blocks the bottleneck step of the converging pathways of oxidative burst triggering. Manipulation of neutrophil membrane composition by CyaA-produced signaling of cAMP thus enables B. pertussis to evade the key innate host defense mechanism of reactive oxygen species mediated killing of bacteria by neutrophils. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2018
Počet záznamů: 1