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A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation
Infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death in human immunodeficiency virus (HIV)(+) individuals, particularly in Sub-Saharan Africa. Management of this deadly co-infection is a significant global health challenge that is exacerbated by the lack of efficient vaccine...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938611/ https://www.ncbi.nlm.nih.gov/pubmed/27391012 http://dx.doi.org/10.1371/journal.pone.0158849 |
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author | Kupz, Andreas Zedler, Ulrike Stäber, Manuela Kaufmann, Stefan H. E. |
author_facet | Kupz, Andreas Zedler, Ulrike Stäber, Manuela Kaufmann, Stefan H. E. |
author_sort | Kupz, Andreas |
collection | PubMed |
description | Infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death in human immunodeficiency virus (HIV)(+) individuals, particularly in Sub-Saharan Africa. Management of this deadly co-infection is a significant global health challenge that is exacerbated by the lack of efficient vaccines against both Mtb and HIV, as well as the lack of reliable and robust animal models for Mtb/HIV co-infection. Here we describe a tractable and reproducible mouse model to study the reactivation dynamics of latent Mtb infection following the loss of CD4(+) T cells as it occurs in HIV-co-infected individuals. Whereas intradermally (i.d.) infected C57BL/6 mice contained Mtb within the local draining lymph nodes, depletion of CD4(+) cells led to progressive systemic spread of the bacteria and induction of lung pathology. To interrogate whether reactivation of Mtb after CD4(+) T cell depletion can be reversed, we employed interleukin (IL)-2/anti-IL-2 complex-mediated cell boost approaches. Although populations of non-CD4 lymphocytes, such as CD8(+) memory T cells, natural killer (NK) cells and double-negative (DN) T cells significantly expanded after IL-2/anti-IL-2 complex treatment, progressive development of bacteremia and pathologic lung alterations could not be prevented. These data suggest that the failure to reverse Mtb reactivation is likely not due to anergy of the expanded cell subsets and rather indicates a limited potential for IL-2-complex-based therapies in the management of Mtb/HIV co-infection. |
format | Online Article Text |
id | pubmed-4938611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-49386112016-07-22 A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation Kupz, Andreas Zedler, Ulrike Stäber, Manuela Kaufmann, Stefan H. E. PLoS One Research Article Infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death in human immunodeficiency virus (HIV)(+) individuals, particularly in Sub-Saharan Africa. Management of this deadly co-infection is a significant global health challenge that is exacerbated by the lack of efficient vaccines against both Mtb and HIV, as well as the lack of reliable and robust animal models for Mtb/HIV co-infection. Here we describe a tractable and reproducible mouse model to study the reactivation dynamics of latent Mtb infection following the loss of CD4(+) T cells as it occurs in HIV-co-infected individuals. Whereas intradermally (i.d.) infected C57BL/6 mice contained Mtb within the local draining lymph nodes, depletion of CD4(+) cells led to progressive systemic spread of the bacteria and induction of lung pathology. To interrogate whether reactivation of Mtb after CD4(+) T cell depletion can be reversed, we employed interleukin (IL)-2/anti-IL-2 complex-mediated cell boost approaches. Although populations of non-CD4 lymphocytes, such as CD8(+) memory T cells, natural killer (NK) cells and double-negative (DN) T cells significantly expanded after IL-2/anti-IL-2 complex treatment, progressive development of bacteremia and pathologic lung alterations could not be prevented. These data suggest that the failure to reverse Mtb reactivation is likely not due to anergy of the expanded cell subsets and rather indicates a limited potential for IL-2-complex-based therapies in the management of Mtb/HIV co-infection. Public Library of Science 2016-07-08 /pmc/articles/PMC4938611/ /pubmed/27391012 http://dx.doi.org/10.1371/journal.pone.0158849 Text en © 2016 Kupz 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kupz, Andreas Zedler, Ulrike Stäber, Manuela Kaufmann, Stefan H. E. A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation |
title | A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation |
title_full | A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation |
title_fullStr | A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation |
title_full_unstemmed | A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation |
title_short | A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation |
title_sort | mouse model of latent tuberculosis infection to study intervention strategies to prevent reactivation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938611/ https://www.ncbi.nlm.nih.gov/pubmed/27391012 http://dx.doi.org/10.1371/journal.pone.0158849 |
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