HIV-1 and SIV Infection Are Associated with Early Loss of Lung Interstitial CD4+ T Cells and Dissemination of Pulmonary Tuberculosis

Abstract

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. : Corleis et al. show that lung parenchymal CD4+ T cells are permissive to HIV-1-dependent cell death. CD4+ T cell loss is highly significant in the interstitium but not the alveolar space, and loss of interstitial CD4+ T cells is associated with extrapulmonary dissemination of M. tuberculosis. Keywords: HIV-1, CD4+ T cells, cell death, tuberculosis, HIV/TB co-infection, lung, BAL