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

doi:10.1016/j.celrep.2019.01.021

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

Cell Rep. 2019 Feb 5;26(6):1409-1418.e5. doi: 10.1016/j.celrep.2019.01.021.

Authors

Björn Corleis¹, Allison N Bucsan², Maud Deruaz³, Vladimir D Vrbanac³, Antonella C Lisanti-Park⁴, Samantha J Gates⁴, Alice H Linder⁴, Jeffrey M Paer⁴, Gregory S Olson⁴, Brittany A Bowman⁴, Abigail E Schiff⁴, Benjamin D Medoff⁵, Andrew M Tager⁶, Andrew D Luster⁷, Shabaana A Khader⁸, Deepak Kaushal⁹, Douglas S Kwon¹⁰

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
² Tulane National Primate Research Center, Covington, LA, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
³ 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.
⁴ Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ 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.
⁶ 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.
⁷ Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
⁸ Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
⁹ Tulane National Primate Research Center, Covington, LA, USA; Southwest National Primate Research Center, San Antonio, TX, USA.
¹⁰ 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.

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.

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

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / pathology
Coinfection / immunology*
Coinfection / pathology
Female
HEK293 Cells
HIV Infections / immunology*
HIV Infections / pathology
HIV-1 / pathogenicity
Humans
Lung / immunology
Lung / microbiology
Lung / pathology
Lung / virology
Macaca mulatta
Mice
Mycobacterium tuberculosis / pathogenicity
Simian Acquired Immunodeficiency Syndrome / immunology*
Simian Acquired Immunodeficiency Syndrome / pathology
Simian Immunodeficiency Virus / pathogenicity
Tuberculosis, Pulmonary / immunology*
Tuberculosis, Pulmonary / pathology

Abstract

Publication types

MeSH terms

Grants and funding