Virulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor.

2.50
Hdl Handle:
http://hdl.handle.net/10029/622075
Title:
Virulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor.
Authors:
Hovingh, Elise S; de Maat, Steven; Cloherty, Alexandra P M; Johnson, Steven; Pinelli, Elena; Maas, Coen; Jongerius, Ilse
Abstract:
Bordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Whooping cough is currently re-emerging worldwide and, therefore, still poses a continuous global health threat. B. pertussis expresses several virulence factors that play a role in evading the human immune response. One of these virulence factors is virulence associated gene 8 (Vag8). Vag8 is a complement evasion molecule that mediates its effects by binding to the complement regulator C1 inhibitor (C1-INH). This regulatory protein is a fluid phase serine protease that controls proenzyme activation and enzyme activity of not only the complement system but also the contact system. Activation of the contact system results in the generation of bradykinin, a pro-inflammatory peptide. Here, the activation of the contact system by B. pertussis was explored. We demonstrate that recombinant as well as endogenous Vag8 enhanced contact system activity by binding C1-INH and attenuating its inhibitory function. Moreover, we show that B. pertussis itself is able to activate the contact system. This activation was dependent on Vag8 production as a Vag8 knockout B. pertussis strain was unable to activate the contact system. These findings show a previously overlooked interaction between the contact system and the respiratory pathogen B. pertussis. Activation of the contact system by B. pertussis may contribute to its pathogenicity and virulence.
Citation:
Virulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor. 2018, 9:1172 Front Immunol
Journal:
Front Immunol 2018; 9(june):1172
Issue Date:
2018
URI:
http://hdl.handle.net/10029/622075
DOI:
10.3389/fimmu.2018.01172
PubMed ID:
29915576
Type:
Article
Language:
en
ISSN:
1664-3224
Appears in Collections:
Miscellaneous

Full metadata record

DC FieldValue Language
dc.contributor.authorHovingh, Elise Sen
dc.contributor.authorde Maat, Stevenen
dc.contributor.authorCloherty, Alexandra P Men
dc.contributor.authorJohnson, Stevenen
dc.contributor.authorPinelli, Elenaen
dc.contributor.authorMaas, Coenen
dc.contributor.authorJongerius, Ilseen
dc.date.accessioned2018-07-17T13:05:17Z-
dc.date.available2018-07-17T13:05:17Z-
dc.date.issued2018-
dc.identifier.citationVirulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor. 2018, 9:1172 Front Immunolen
dc.identifier.issn1664-3224-
dc.identifier.pmid29915576-
dc.identifier.doi10.3389/fimmu.2018.01172-
dc.identifier.urihttp://hdl.handle.net/10029/622075-
dc.description.abstractBordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Whooping cough is currently re-emerging worldwide and, therefore, still poses a continuous global health threat. B. pertussis expresses several virulence factors that play a role in evading the human immune response. One of these virulence factors is virulence associated gene 8 (Vag8). Vag8 is a complement evasion molecule that mediates its effects by binding to the complement regulator C1 inhibitor (C1-INH). This regulatory protein is a fluid phase serine protease that controls proenzyme activation and enzyme activity of not only the complement system but also the contact system. Activation of the contact system results in the generation of bradykinin, a pro-inflammatory peptide. Here, the activation of the contact system by B. pertussis was explored. We demonstrate that recombinant as well as endogenous Vag8 enhanced contact system activity by binding C1-INH and attenuating its inhibitory function. Moreover, we show that B. pertussis itself is able to activate the contact system. This activation was dependent on Vag8 production as a Vag8 knockout B. pertussis strain was unable to activate the contact system. These findings show a previously overlooked interaction between the contact system and the respiratory pathogen B. pertussis. Activation of the contact system by B. pertussis may contribute to its pathogenicity and virulence.en
dc.language.isoenen
dc.rightsArchived with thanks to Frontiers in immunologyen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleVirulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor.en
dc.typeArticleen
dc.identifier.journalFront Immunol 2018; 9(june):1172en

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