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

Björn Corleis, Allison N. Bucsan, Maud Deruaz, Vladimir D. Vrbanac, Antonella C. Lisanti-Park, Samantha J. Gates, Alice H. Linder, Jeffrey M. Paer, Gregory S. Olson, Brittany A. Bowman, Abigail E. Schiff, Benjamin D. Medoff, Andrew M. Tager, Andrew D. Luster, Shabaana A. Khader, Deepak Kaushal, Douglas S. Kwon

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1409-1418.e5
JournalCell Reports
Volume26
Issue number6
DOIs
StatePublished - Feb 5 2019

Keywords

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

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