Cutting Edge: In Vivo Induction of Integrated HIV-1 Expression by Mycobacteria Is Critically Dependent on Toll-Like Receptor 2 1

Cutting Edge: In Vivo Induction of Integrated HIV-1 Expression by Mycobacteria Is Critically Dependent on Toll-Like Receptor 2 1
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最前沿:分枝杆菌在体内诱导整合 HIV-1 表达严重依赖于 Toll 样受体 2 1

DOI:
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发表时间:
2003
影响因子:
4.4
通讯作者:
A. Sher
A. Sher
中科院分区:
医学2区
文献类型:
--
作者:
A. Báfica;C. Scanga;M. Schito;S. Hieny;A. Sher

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在HIV-1和结核分枝杆菌共同流行的人群中,分枝杆菌感染被认为是艾滋病进展的一个可能因素。为了支持这一概念,我们以前已经表明,HIV-1转基因(Tg)小鼠感染分枝杆菌显示增强病毒基因和蛋白质的表达。在这项研究中,我们证明了在这个模型中观察到的HIV-1的诱导依赖于Toll样受体2(TLR 2),一种已知参与分枝杆菌-宿主相互作用的模式识别受体。来自TLR 2缺陷型HIV-1-Tg小鼠(Tg/TLR 2 −/−)的脾细胞被发现在响应活M.结核或鸟分枝杆菌以及某些分枝杆菌产物。重要的是,在体内分枝杆菌感染后,Tg/TLR 2 −/−小鼠未能表现出野生型Tg动物所表现出的增强的HIV-1 gag/env mRNA和p24蛋白合成。总之,这些结果表明TLR 2在分枝杆菌合并感染激活HIV-1表达中起着至关重要的作用。
Mycobacterial infection has been implicated as a possible factor in AIDS progression in populations where HIV-1 and Mycobacterium tuberculosis are coendemic. In support of this concept, we have previously shown that HIV-1-transgenic (Tg) mice infected with mycobacteria display enhanced viral gene and protein expression. In this study, we demonstrate that the induction of HIV-1 observed in this model is dependent on Toll-like receptor 2 (TLR2), a pattern recognition receptor known to be involved in mycobacteria-host interaction. Spleen cells from HIV-1-Tg mice deficient in TLR2 (Tg/TLR2−/−) were found to be completely defective in p24 production induced in response to live M. tuberculosis or Mycobacterium avium as well as certain mycobacterial products. Importantly, following in vivo mycobacterial infection, Tg/TLR2−/− mice failed to display the enhanced HIV-1 gag/env mRNA and p24 protein synthesis exhibited by wild-type Tg animals. Together, these results argue that TLR2 plays a crucial role in the activation of HIV-1 expression by mycobacterial coinfections.
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