Increased expression of suppressor of cytokine signaling-1 (SOCS-1): A mechanism for dysregulated T helper-1 responses in HIV-1 disease

被引：28

作者：

Yadav, Anjana ^{[1
]}

Fitzgerald, Phillip ^{[1
]}

Sajadi, Mohammad M. ^{[1
]}

Gilliam, Bruce ^{[1
]}

Lafferty, Mark K. ^{[2
]}

Redfield, Robert ^{[1
]}

Reid, William ^{[1
,2
]}

机构：

[1] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA

[2] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA

来源：

VIROLOGY | 2009年 / 385卷 / 01期

关键词：

HIV-1; Transgenic rat; SOCS-1; IFN-gamma-IL-12; signaling; IRF-1; IL-12R beta 1; INTERFERON-GAMMA; TRANSGENIC RAT; T-CELLS; DENDRITIC CELLS; BETA; INTERLEUKIN-12; INFECTION; DIFFERENTIATION; TRANSCRIPTION; ACTIVATION;

D O I：

10.1016/j.virol.2008.11.039

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Maintenance of Th1 responses and dendritic cell (DC) functions are compromised in HIV-1 infected individuals. To better understand these immune abnormalities, we developed an HIV-1 transgenic (Tg) rat. We report that Tg DCs induce elevated levels of SOCS-1 and secrete decreased IL-12p40 and elevated levels of IL-10 following TLR-4 stimulation by LPS. This leads to further induction of SOCS-1 by IL-10 and decreased IFN-gamma-mediated induction of interferon response factor (IRF)-1 and IL-12R beta 1 expression in CD4+T cells and to decreased IL-12-induction of IFN-gamma production by Th1 polarized T cells. We also show that SOCS-1 is elevated in CD4+T cells from HIV-1 infected progressors, and is correlated with defective induction of IRF-1 following IFN-gamma stimulation, compared with healthy controls and HIV-1 natural viral suppressor (NVS) patients. These results suggest a link between high levels of SOCS-1, defects in innate immunity and adaptive Th1 responses that may be reflected in the loss of Th1 immune competence observed with AIDS patients. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：126 / 133

页数：8

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