Tubular cell HIV-entry through apoptosed CD4 T cells: A novel pathway

被引:17
作者
Singh, Priyanka [1 ]
Goel, Hersh [1 ]
Husain, Mohammad [1 ]
Lan, Xiqian [1 ]
Mikulak, Joanna [1 ]
Malthotra, Ashwani [1 ]
Teichberg, Saul [1 ]
Schmidtmayerova, Helena [1 ]
Singhal, Pravin C. [1 ]
机构
[1] Hofstra N Shore Long Isl Jewish Med Sch, Feinstein Inst Med Res, Ctr Excellence Immunol & Inflammat, New Hyde Pk, NY USA
基金
美国国家卫生研究院;
关键词
Human proximal tubular cells; HIV; T cell; Apoptosis; PD-1; receptor; PD-L1; Phagocytosis; Reactive oxygen species; IMMUNODEFICIENCY-VIRUS TYPE-1; HEPATITIS-B-VIRUS; EPITHELIAL-CELLS; EXPRESSION; PD-L1; ANTIGEN; B7-H1; INTERNALIZATION; PHAGOCYTOSIS; RECOGNITION;
D O I
10.1016/j.virol.2012.09.009
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We hypothesized that HIV-1 may enter tubular cells by phagocytosis of apoptotic fragments of HIV-1-infected T cells infiltrating tubular interstitium. The study was designed to evaluate the interaction of programmed death-1 (PD-1) receptors on CD4 T cells and programmed death ligand-1 (PD-L1) on tubular cells (HK2 and HRFTEC, primary tubular cells). Co-cultivation of HIV-1 infected lymphocytes (HIV-LY) with HK2s/HRPTECs resulted in T cell apoptosis, uptake of the apoptosed HIV-LY by HK2s/HRPTECs, tubular cell activation and HIV expression. Cytochalasin-B inhibited tubular cell HIV-LY uptake and anti-PD-L1 antibody inhibited HIV-LY apoptosis and tubular cell HIV-LY uptake, activation and HIV expression. These observations do indicate induction of apoptosis of T cells due to interaction of PD-1 and PD-L1 upon co-cultivation and subsequent phygocytosis of HIV-laden apoptotic bodies by tubular cells and thus the transfer of HIV-1 into tubular cells. These findings identify a novel pathway that facilitates HIV-1 entry into tubular cell. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:68 / 77
页数:10
相关论文
共 47 条
[1]   Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes [J].
Agata, Y ;
Kawasaki, A ;
Nishimura, H ;
Ishida, Y ;
Tsubata, T ;
Yagita, H ;
Honjo, T .
INTERNATIONAL IMMUNOLOGY, 1996, 8 (05) :765-772
[2]   INHIBITION OF PHAGOCYTOSIS AND PLASMA-MEMBRANE MOBILITY OF CULTIVATED MACROPHAGE BY CYTOCHALASIN-B - ROLE OF SUBPLASMALEMMAL MICROFILAMENTS [J].
AXLINE, SG ;
REAVEN, EP .
JOURNAL OF CELL BIOLOGY, 1974, 62 (03) :647-659
[3]   Restoring function in exhausted CD8 T cells during chronic viral infection [J].
Barber, DL ;
Wherry, EJ ;
Masopust, D ;
Zhu, BG ;
Allison, JP ;
Sharpe, AH ;
Freeman, GJ ;
Ahmed, R .
NATURE, 2006, 439 (7077) :682-687
[4]   PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells [J].
Blank, C ;
Brown, I ;
Peterson, AC ;
Spiotto, M ;
Iwai, Y ;
Honjo, T ;
Gajewski, TF .
CANCER RESEARCH, 2004, 64 (03) :1140-1145
[5]   Blockade of programmed death-1 Ligands on dendritic cells enhances T cell activation and cytokine production [J].
Brown, JA ;
Dorfman, DM ;
Ma, FR ;
Sullivan, EL ;
Munoz, O ;
Wood, CR ;
Greenfield, EA ;
Freeman, GJ .
JOURNAL OF IMMUNOLOGY, 2003, 170 (03) :1257-1266
[6]   Controversies in the pathogenesis of HIV-associated renal diseases [J].
Bruggeman, Leslie A. ;
Nelson, Peter J. .
NATURE REVIEWS NEPHROLOGY, 2009, 5 (10) :575-582
[7]   Virological Synapses Allow HIV-1 Uptake and Gene Expression in Renal Tubular Epithelial Cells [J].
Chen, Ping ;
Chen, Benjamin K. ;
Mosoian, Arevik ;
Hays, Thomas ;
Ross, Michael J. ;
Klotman, Paul E. ;
Klotman, Mary E. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2011, 22 (03) :496-507
[8]   Cervical and prostate primary epithelial cells are not productively infected but sequester human immunodeficiency virus type 1 [J].
Dezzutti, CS ;
Guenthner, PC ;
Cummins, JE ;
Cabrera, T ;
Marshall, JH ;
Dillberger, A ;
Lal, RB .
JOURNAL OF INFECTIOUS DISEASES, 2001, 183 (08) :1204-1213
[9]   PD-L1 is expressed by human renal tubular epithelial cells and suppresses T cell cytokine synthesis [J].
Ding, HL ;
Wu, XF ;
Gao, W .
CLINICAL IMMUNOLOGY, 2005, 115 (02) :184-191
[10]   B7-H1 determines accumulation and deletion of intrahepatic CD8+ T lymphocytes [J].
Dong, HD ;
Zhu, GF ;
Tamada, K ;
Flies, DB ;
van Deursen, JMA ;
Chen, LP .
IMMUNITY, 2004, 20 (03) :327-336