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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 1

Comparison of CD4+ T cell–sparing SIVmac239ΔGY and antibody-mediated CD4+ T cell depletion using CD4R1 in Mtb-infected NHPs.

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Comparison of CD4+ T cell–sparing SIVmac239ΔGY and antibody-mediated CD4...
(A) Study outline. (B) Serum CRP levels at necropsy. (C) Percentage of temperature increase (°C) and (D) percentage of weight loss (kg) compared with baseline. (E) Ratio of neutrophils to lymphocytes in clinical blood. Bacterial burden at necropsy measured in (F) BAL, (G) lung, and (H) bronchial lymph nodes. (I) CXR scores established by veterinary clinicians for pneumonia. (J) Percentage of lung involvement determined by board-certified veterinary pathologists. (K) Peak plasma viral loads (PVLs) measured at peak. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001, 1-way ANOVA with Tukey’s multiple testing correction. C–E represent mean, and B and F–J represent mean ± SEM.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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