@article{9aee1eafb40c4f54878227301d440576,
title = "HIV-1 and SIV Infection Are Associated with Early Loss of Lung Interstitial CD4+ T Cells and Dissemination of Pulmonary Tuberculosis",
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",
author = "Bj{\"o}rn Corleis and Bucsan, {Allison N.} and Maud Deruaz and Vrbanac, {Vladimir D.} and Lisanti-Park, {Antonella C.} and Gates, {Samantha J.} and Linder, {Alice H.} and Paer, {Jeffrey M.} and Olson, {Gregory S.} and Bowman, {Brittany A.} and Schiff, {Abigail E.} and Medoff, {Benjamin D.} and Tager, {Andrew M.} and Luster, {Andrew D.} and Khader, {Shabaana A.} and Deepak Kaushal and Kwon, {Douglas S.}",
note = "Funding Information: D.S.K. and B.D.M. were supported by the NHLBI ( U01HL121827 ) and D.S.K. by the Burroughs Wellcome Fund . A.D.L. was supported by AI040618 and AI112521 . This work was also supported by the Human Immune System Mouse Core subcontract (A.M.T., principal investigator) from the NIH Harvard University Center for AIDS Research (CFAR) and NIH/NIAID P30 AI060354 (Dr. Bruce Walker, principal investigator). A.E.S. was supported by awards T32GM007753 and F30HL134566-02 from the National Institute of General Medical Sciences . D.K. and S.A.K. were supported by AI111914 , AI123780 , AI111943 , AI089323 , HL106790 , and RR026006 . We would like to thank the pathology lab at MGH for tissue collection, Dr. Thorsten Mempel and Dr. Thomas Murooka for kindly providing NL4-3 GFP HIV-1, and the CFAR humanized mouse core for their service. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = feb,
day = "5",
doi = "10.1016/j.celrep.2019.01.021",
language = "English",
volume = "26",
pages = "1409--1418.e5",
journal = "Cell Reports",
issn = "2211-1247",
number = "6",
}