Immune quiescence: a model of protection against HIV infection.
Immune quiescence: a model of protection against HIV infection.
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DOI：
10.1186/1742-4690-10-141
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发表时间：
2013-11-20
期刊：
影响因子：
3.3
通讯作者：
Fowke KR
中科院分区：
文献类型：
--
作者：
Card CM;Ball TB;Fowke KR
异常免疫激活与HIV疾病进展密切相关，但对免疫激活如何改变对HIV感染的易感性知之甚少。艾滋病毒感染的易感性因人而异，但艾滋病毒传播的免疫决定因素还不清楚。在这里，我们从临床试验和HIV暴露血清阴性（HESN）队列中的HIV传播研究中获得证据，这些证据表明免疫激活升高是获得HIV的风险因素。我们提出了一个模型的基础上的低基线免疫激活称为免疫静止表型的感染保护。HESN外周和生殖器粘膜中T细胞活化标志物表达减少、低水平的广义基因转录和低水平的促炎细胞因子和趋化因子产生证明了免疫静止。由于HIV优先在活化的CD 4 + T细胞中复制，免疫静止可能通过限制HIV靶细胞的可用性来保护免受感染。虽然免疫静止的决定因素尚不清楚，但已经确定了几个可能参与驱动这种表型的潜在因素。HESN显示具有升高比例的调节性T细胞（T细胞），已知其抑制T细胞活化。同样，已经发现参与控制生殖道炎症的蛋白质在HESN中升高。此外，干扰素调节因子1（IRF-1）的表达减少在HESN作为遗传多态性和差异表观遗传调节的结果。由于IRF-1是免疫应答的重要调节剂，因此它可能在维持免疫静止中起作用。基于此模型，我们提出了一种新的途径，艾滋病毒预防的基础上减少宿主粘膜免疫激活的目标。
Aberrant immune activation is a strong correlate of HIV disease progression, but little is known about how immune activation alters susceptibility to HIV infection. Susceptibility to HIV infection varies between individuals, but the immunological determinants of HIV transmission are not well understood. Here, we present evidence from studies of HIV transmission in the context of clinical trials and HIV-exposed seronegative (HESN) cohorts that implicates elevated immune activation as a risk factor for acquiring HIV. We propose a model of protection from infection based on a phenotype of low baseline immune activation referred to as immune quiescence. Immune quiescence is evidenced by reduced expression of T cell activation markers, low levels of generalized gene transcription and low levels of proinflammatory cytokine and chemokine production in the periphery and genital mucosa of HESN. Since HIV preferentially replicates in activated CD4+ T cells, immune quiescence may protect against infection by limiting HIV target cell availability. Although the determinants of immune quiescence are unclear, several potential factors have been identified that may be involved in driving this phenotype. HESN were shown to have elevated proportions of regulatory T cells (Tregs), which are known to suppress T cell activation. Likewise, proteins involved in controlling inflammation in the genital tract have been found to be elevated in HESN. Furthermore, expression of interferon regulatory factor 1 (IRF-1) is reduced in HESN as a consequence of genetic polymorphisms and differential epigenetic regulation. Since IRF-1 is an important regulator of immune responses, it may play a role in maintaining immune quiescence. Based on this model, we propose a novel avenue for HIV prevention targeted based on reducing host mucosal immune activation.
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影响因子：
8
作者：
Genesca, M.;Skinner, P. J.;Miller, C. J.
通讯作者：
Miller, C. J.
影响因子：
4.4
作者：
Kaul, R;Plummer, FA;Rowland-Jones, SL
通讯作者：
Rowland-Jones, SL
影响因子：
6.4
作者：
Camara, Makhtar;Dieye, Tandakha Ndiaye;Jennes, Wim
通讯作者：
Jennes, Wim
影响因子：
4.4
作者：
Antons, Amanda K.;Wang, Rui;Unutmaz, Derya
通讯作者：
Unutmaz, Derya
影响因子：
4.6
作者：
Hunt, Peter W.
通讯作者：
Hunt, Peter W.