Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice

Interleukin (IL)-17 is emerging as an important cytokine in vaccine-induced protection against tuberculosis disease in animal models. Here we show that compared to parenteral delivery, BCG delivered mucosally enhances cytokine production, including interferon gamma and IL-17, in the lungs. Furthermo...

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Auteurs principaux: Griffiths, K, Stylianou, E, Poyntz, H, Betts, G, Fletcher, H, McShane, H
Format: Journal article
Langue:English
Publié: Public Library of Science 2013
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author Griffiths, K
Stylianou, E
Poyntz, H
Betts, G
Fletcher, H
McShane, H
author_facet Griffiths, K
Stylianou, E
Poyntz, H
Betts, G
Fletcher, H
McShane, H
author_sort Griffiths, K
collection OXFORD
description Interleukin (IL)-17 is emerging as an important cytokine in vaccine-induced protection against tuberculosis disease in animal models. Here we show that compared to parenteral delivery, BCG delivered mucosally enhances cytokine production, including interferon gamma and IL-17, in the lungs. Furthermore, we find that cholera toxin, delivered mucosally along with BCG, further enhances IL-17 production by CD4+ T cells over mucosal BCG alone both in the lungs and systemically. This boosting effect of CT is also observed using a vaccine regimen of BCG followed by the candidate vaccine MVA85A. Using a murine Mycobacterium tuberculosis (M.tb) aerosol challenge model, we demonstrate the ability of cholera toxin delivered at the time of a priming BCG vaccination to improve protection against tuberculosis disease in a manner at least partially dependent on the observed increase in IL-17. This observed increase in IL-17 in the lungs has no adverse effect on lung pathology following M.tb challenge, indicating that IL-17 can safely be boosted in murine lungs in a vaccine/M.tb challenge setting.
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spelling oxford-uuid:242c46b2-a08d-4e76-95d6-aae8377e2d762022-03-26T11:48:28ZCholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in miceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:242c46b2-a08d-4e76-95d6-aae8377e2d76EnglishSymplectic Elements at OxfordPublic Library of Science2013Griffiths, KStylianou, EPoyntz, HBetts, GFletcher, HMcShane, HInterleukin (IL)-17 is emerging as an important cytokine in vaccine-induced protection against tuberculosis disease in animal models. Here we show that compared to parenteral delivery, BCG delivered mucosally enhances cytokine production, including interferon gamma and IL-17, in the lungs. Furthermore, we find that cholera toxin, delivered mucosally along with BCG, further enhances IL-17 production by CD4+ T cells over mucosal BCG alone both in the lungs and systemically. This boosting effect of CT is also observed using a vaccine regimen of BCG followed by the candidate vaccine MVA85A. Using a murine Mycobacterium tuberculosis (M.tb) aerosol challenge model, we demonstrate the ability of cholera toxin delivered at the time of a priming BCG vaccination to improve protection against tuberculosis disease in a manner at least partially dependent on the observed increase in IL-17. This observed increase in IL-17 in the lungs has no adverse effect on lung pathology following M.tb challenge, indicating that IL-17 can safely be boosted in murine lungs in a vaccine/M.tb challenge setting.
spellingShingle Griffiths, K
Stylianou, E
Poyntz, H
Betts, G
Fletcher, H
McShane, H
Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice
title Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice
title_full Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice
title_fullStr Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice
title_full_unstemmed Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice
title_short Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice
title_sort cholera toxin enhances vaccine induced protection against mycobacterium tuberculosis challenge in mice
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AT bettsg choleratoxinenhancesvaccineinducedprotectionagainstmycobacteriumtuberculosischallengeinmice
AT fletcherh choleratoxinenhancesvaccineinducedprotectionagainstmycobacteriumtuberculosischallengeinmice
AT mcshaneh choleratoxinenhancesvaccineinducedprotectionagainstmycobacteriumtuberculosischallengeinmice