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Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection
Allison N. Bucşan, … , Shabaana A. Khader, Deepak Kaushal
Allison N. Bucşan, … , Shabaana A. Khader, Deepak Kaushal
Published September 3, 2019
Citation Information: J Clin Invest. 2019;129(12):5254-5260. https://doi.org/10.1172/JCI125810.
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Concise Communication AIDS/HIV Infectious disease

Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection

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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.

Authors

Allison N. Bucşan, Ayan Chatterjee, Dhiraj K. Singh, Taylor W. Foreman, Tae-Hyung Lee, Breanna Threeton, Melanie G. Kirkpatrick, Mushtaq Ahmed, Nadia Golden, Xavier Alvarez, James A. Hoxie, Smriti Mehra, Jyothi Rengarajan, Shabaana A. Khader, Deepak Kaushal

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Figure 2

CD4+ T cells are preserved in Mtb/SIVΔGY coinfection and ablated in Mtb/CD4R1 administration.

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CD4+ T cells are preserved in Mtb/SIVΔGY coinfection and ablated in Mtb/...
CD4+ T cell quantification at necropsy SIVΔGY coinfection in (A) peripheral blood, (B) BAL, and (C) lungs. CD4+ T cell quantification in (D) peripheral blood, (E) BAL, and (F) lungs during CD4R1 administration (n = 8, red). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001, 1-way ANOVA with Tukey’s multiple testing correction. Confocal images of CD4+ cells (red) and nuclei (gray) in formalin-fixed, paraffin-embedded tissue (FFPE) from (G) CD4R1-administered, (H) SIVΔGY-coinfected, and (I) SIVmac239 coinfected nonreactivator, and (J) reactivator NHPs. (K) Quantification of CD4+ cells per nuclei stained in 9 lung sections from a single slide, 1 animal per group. Data represent mean ± SEM.

Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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