Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load

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).

[img]
Preview
PDF
Published Version
Available under License : See the attached license file.

Download (1MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

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.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Diedrich, CRcollindiedrich@pitt.eduCRD64
Mattila, JTjmattila@pitt.eduJMATTILA
Klein, Eeklein@pitt.eduEKLEIN
Janssen, C
Phuah, J
Sturgeon, TJsturgeon@pitt.eduSTURGEON
Montelaro, RCrmont@pitt.eduRMONT
Lin, PLpll7@pitt.eduPLL7
Flynn, JAL
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorWilkinson, Robert J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item