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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.

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
Cell reports | 2019

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.

Pubmed ID: 30726727

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI111914
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI123047
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI112521
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI040618
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI089323
  • Agency: NIH HHS, United States
    Id: P51 OD011133
  • Agency: NCRR NIH HHS, United States
    Id: R21 RR026006
  • Agency: NIAID NIH HHS, United States
    Id: P30 AI060354
  • Agency: NHLBI NIH HHS, United States
    Id: F30 HL134566
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI123780
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL106790
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK043351
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007753
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI111943
  • Agency: NIAID NIH HHS, United States
    Id: R37 AI040618
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL121827

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