Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection.
J Clin Invest
; 129(12): 5254-5260, 2019 12 02.
Article
in En
| MEDLINE
| ID: mdl-31479428
ABSTRACT
HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in HIV-coinfected individuals.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Simian Acquired Immunodeficiency Syndrome
/
Latent Tuberculosis
/
Coinfection
Limits:
Animals
Language:
En
Journal:
J Clin Invest
Year:
2019
Document type:
Article
Affiliation country:
United States