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
Affiliations
Björn Corleis
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Corresponding author
Allison N. Bucsan
Tulane National Primate Research Center, Covington, LA, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA
Maud Deruaz
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
Vladimir D. Vrbanac
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
Antonella C. Lisanti-Park
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Samantha J. Gates
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Alice H. Linder
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Jeffrey M. Paer
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Gregory S. Olson
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Brittany A. Bowman
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Abigail E. Schiff
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Benjamin D. Medoff
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
Andrew M. Tager
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
Andrew D. Luster
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
Shabaana A. Khader
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
Deepak Kaushal
Tulane National Primate Research Center, Covington, LA, USA; Southwest National Primate Research Center, San Antonio, TX, USA
Douglas S. Kwon
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA
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
