Diedrich, CR and Mattila, JT and Klein, E and Janssen, C and Phuah, J and Sturgeon, TJ and Montelaro, RC and Lin, PL and Flynn, JAL
(2010)
Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load.
PLoS ONE, 5 (3).
Abstract
HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb) infection are at significantly greater risk of reactivation tuberculosis (TB) than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV). Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks) had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection. © 2010 Diedrich et al.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID  |
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Editor | Wilkinson, Robert J. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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Centers: |
Other Centers, Institutes, Offices, or Units > Center for Vaccine Research |
Date: |
10 March 2010 |
Date Type: |
Publication |
Journal or Publication Title: |
PLoS ONE |
Volume: |
5 |
Number: |
3 |
DOI or Unique Handle: |
10.1371/journal.pone.0009611 |
Refereed: |
Yes |
MeSH Headings: |
Animals; Antibodies, Viral--administration & dosage; Antibodies, Viral--immunology; CD4-Positive T-Lymphocytes--cytology; Comorbidity; Flow Cytometry--methods; Granuloma--metabolism; Immune System; Interferon-gamma--metabolism; Macaca fascicularis; Simian Acquired Immunodeficiency Syndrome--complications; Simian immunodeficiency virus--immunology; T-Lymphocytes--immunology; Viral Load |
Other ID: |
NLM PMC2835744 |
PubMed Central ID: |
PMC2835744 |
PubMed ID: |
20224771 |
Date Deposited: |
03 Aug 2012 18:44 |
Last Modified: |
20 Jul 2019 14:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/13337 |
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