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BCG-Mediated Protection against Mycobacterium ulcerans Infection in the Mouse

BACKGROUND: Vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) is widely used to reduce the risk of childhood tuberculosis and has been reported to have efficacy against two other mycobacterial diseases, leprosy and Buruli ulcer caused by M. ulcerans (Mu). Studies in experimental mod...

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Detalles Bibliográficos
Autores principales: Converse, Paul J., Almeida, Deepak V., Nuermberger, Eric L., Grosset, Jacques H.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057947/
https://www.ncbi.nlm.nih.gov/pubmed/21423646
http://dx.doi.org/10.1371/journal.pntd.0000985
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author Converse, Paul J.
Almeida, Deepak V.
Nuermberger, Eric L.
Grosset, Jacques H.
author_facet Converse, Paul J.
Almeida, Deepak V.
Nuermberger, Eric L.
Grosset, Jacques H.
author_sort Converse, Paul J.
collection PubMed
description BACKGROUND: Vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) is widely used to reduce the risk of childhood tuberculosis and has been reported to have efficacy against two other mycobacterial diseases, leprosy and Buruli ulcer caused by M. ulcerans (Mu). Studies in experimental models have also shown some efficacy against infection caused by Mu. In mice, most studies use the C57BL/6 strain that is known to develop good cell-mediated protective immunity. We hypothesized that there may be differences in vaccination efficacy between C57BL/6 and the less resistant BALB/c strain. METHODS: We evaluated BCG vaccine efficacy against challenge with ∼3×10(5) M. ulcerans in the right hind footpad using three strains: initially, the Australian type strain, designated Mu1617, then, a Malaysian strain, Mu1615, and a recent Ghanaian isolate, Mu1059. The latter two strains both produce mycolactone while the Australian strain has lost that capacity. CFU of both BCG and Mu and splenocyte cytokine production were determined at intervals after infection. Time to footpad swelling was assessed weekly. PRINCIPAL FINDINGS: BCG injection induced visible scars in 95.5% of BALB/c mice but only 43.4% of C57BL/6 mice. BCG persisted at higher levels in spleens of BALB/c than C57BL/6 mice. Vaccination delayed swelling and reduced Mu CFU in BALB/c mice, regardless of challenge strain. However, vaccination was only protective against Mu1615 and Mu1617 in C57BL/6 mice. Possible correlates of the better protection of BALB/c mice included 1) the near universal development of BCG scars in these mice compared to less frequent and smaller scars observed in C57BL/6 mice and 2) the induction of sustained cytokine, e.g., IL17, production as detected in the spleens of BALB/c mice whereas cytokine production was significantly reduced, e.g., IL17, or transient, e.g., Ifnγ, in the spleens of C57BL/6 mice. CONCLUSIONS: The efficacy of BCG against M. ulcerans, in particular, and possibly mycobacteria in general, may vary due to differences in both host and pathogen.
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spelling pubmed-30579472011-03-21 BCG-Mediated Protection against Mycobacterium ulcerans Infection in the Mouse Converse, Paul J. Almeida, Deepak V. Nuermberger, Eric L. Grosset, Jacques H. PLoS Negl Trop Dis Research Article BACKGROUND: Vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) is widely used to reduce the risk of childhood tuberculosis and has been reported to have efficacy against two other mycobacterial diseases, leprosy and Buruli ulcer caused by M. ulcerans (Mu). Studies in experimental models have also shown some efficacy against infection caused by Mu. In mice, most studies use the C57BL/6 strain that is known to develop good cell-mediated protective immunity. We hypothesized that there may be differences in vaccination efficacy between C57BL/6 and the less resistant BALB/c strain. METHODS: We evaluated BCG vaccine efficacy against challenge with ∼3×10(5) M. ulcerans in the right hind footpad using three strains: initially, the Australian type strain, designated Mu1617, then, a Malaysian strain, Mu1615, and a recent Ghanaian isolate, Mu1059. The latter two strains both produce mycolactone while the Australian strain has lost that capacity. CFU of both BCG and Mu and splenocyte cytokine production were determined at intervals after infection. Time to footpad swelling was assessed weekly. PRINCIPAL FINDINGS: BCG injection induced visible scars in 95.5% of BALB/c mice but only 43.4% of C57BL/6 mice. BCG persisted at higher levels in spleens of BALB/c than C57BL/6 mice. Vaccination delayed swelling and reduced Mu CFU in BALB/c mice, regardless of challenge strain. However, vaccination was only protective against Mu1615 and Mu1617 in C57BL/6 mice. Possible correlates of the better protection of BALB/c mice included 1) the near universal development of BCG scars in these mice compared to less frequent and smaller scars observed in C57BL/6 mice and 2) the induction of sustained cytokine, e.g., IL17, production as detected in the spleens of BALB/c mice whereas cytokine production was significantly reduced, e.g., IL17, or transient, e.g., Ifnγ, in the spleens of C57BL/6 mice. CONCLUSIONS: The efficacy of BCG against M. ulcerans, in particular, and possibly mycobacteria in general, may vary due to differences in both host and pathogen. Public Library of Science 2011-03-15 /pmc/articles/PMC3057947/ /pubmed/21423646 http://dx.doi.org/10.1371/journal.pntd.0000985 Text en Converse et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Converse, Paul J.
Almeida, Deepak V.
Nuermberger, Eric L.
Grosset, Jacques H.
BCG-Mediated Protection against Mycobacterium ulcerans Infection in the Mouse
title BCG-Mediated Protection against Mycobacterium ulcerans Infection in the Mouse
title_full BCG-Mediated Protection against Mycobacterium ulcerans Infection in the Mouse
title_fullStr BCG-Mediated Protection against Mycobacterium ulcerans Infection in the Mouse
title_full_unstemmed BCG-Mediated Protection against Mycobacterium ulcerans Infection in the Mouse
title_short BCG-Mediated Protection against Mycobacterium ulcerans Infection in the Mouse
title_sort bcg-mediated protection against mycobacterium ulcerans infection in the mouse
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057947/
https://www.ncbi.nlm.nih.gov/pubmed/21423646
http://dx.doi.org/10.1371/journal.pntd.0000985
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