HIV-1 和 SIV 感染与肺间质 CD4+T 细胞的早期丢失和肺结核的播散有关。
HIV-1 and SIV Infection Are Associated with Early Loss of Lung Interstitial CD4+ T Cells and Dissemination of Pulmonary Tuberculosis.
机构信息
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Tulane National Primate Research Center, Covington, LA, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
出版信息
Cell Rep. 2019 Feb 5;26(6):1409-1418.e5. doi: 10.1016/j.celrep.2019.01.021.
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.
肺间质 CD4+T 细胞对于预防肺部感染至关重要，但在 HIV-1 感染期间，该群体的命运尚未得到充分描述。我们在人类肺组织、人源化小鼠以及结核分枝杆菌（Mycobacterium tuberculosis，Mtb）/猴免疫缺陷病毒（Simian Immunodeficiency Virus，SIV）合并感染的非人类灵长类动物模型中研究了 HIV-1 感染背景下的 CD4+T 细胞。感染 CCR5 嗜性 HIV-1 或 SIV 会导致肺间质 CD4+T 细胞严重且快速地耗竭，而血液或肺肺泡 CD4+T 细胞不受影响。这伴随着这些细胞在体外和体内产生高水平的 HIV-1。重要的是，在 SIV 感染早期，肺间质 CD4+T 细胞的耗竭与肺部 Mtb 感染播散的增加有关。我们表明，肺间质 CD4+T 细胞是 HIV-1 和 SIV 感染的有效靶标，导致其早期耗竭和播散性结核的风险增加。
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