Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection
Citation: Bucşan, A. N., Chatterjee, A., Singh, D. K., Foreman, T. W., Lee, T.-H., Threeton, B., Kirkpatrick, M. G., Ahmed, M., Golden, N., Alvarez, X., Hoxie, J. A., Mehra, S., Rengarajan, J., Khader, S. A., & Kaushal, D. (2019). Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection. The Journal of Clinical Investigation, 129(12), 5254–5260. https://doi.org/10.1172/JCI125810
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.
Author(s): Journal of Clinical Investigation
Resource Type: Journal Articles