Cell Reports
Volume 26, Issue 6, 5 February 2019, Pages 1409-1418.e5
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HIV-1 and SIV Infection Are Associated with Early Loss of Lung Interstitial CD4+ T Cells and Dissemination of Pulmonary Tuberculosis

https://doi.org/10.1016/j.celrep.2019.01.021Get rights and content
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Highlights

  • Lung interstitial CD4+ T cells are highly permissive to HIV-1-induced cell death

  • Alveolar CD4+ T cell numbers are not significantly altered with HIV-1 infection

  • SIV infection leads to interstitial CD4+ T cell depletion during pulmonary TB

  • Lung interstitial CD4+ T cell loss is associated with disseminated TB

Summary

Lung interstitial CD4+ T cells are critical for protection against pulmonary infections, but the fate of this population during HIV-1 infection is not well described. We studied CD4+ T cells in the setting of HIV-1 infection in human lung tissue, humanized mice, and a Mycobacterium tuberculosis (Mtb)/simian immunodeficiency virus (SIV) nonhuman primate co-infection model. Infection with a CCR5-tropic strain of HIV-1 or SIV results in severe and rapid loss of lung interstitial CD4+ T cells but not blood or lung alveolar CD4+ T cells. This is accompanied by high HIV-1 production in these cells in vitro and in vivo. Importantly, during early SIV infection, loss of lung interstitial CD4+ T cells is associated with increased dissemination of pulmonary Mtb infection. We show that lung interstitial CD4+ T cells serve as an efficient target for HIV-1 and SIV infection that leads to their early depletion and an increased risk of disseminated tuberculosis.

Keywords

HIV-1
CD4+ T cells
cell death
tuberculosis
HIV/TB co-infection
lung
BAL

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