HIV-1 activates macrophages independent of Toll-like receptors.
HIV-1 activates macrophages independent of Toll-like receptors.
复制标题
DOI：
10.1371/journal.pone.0003664
复制
发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Goodenow MM
中科院分区：
文献类型：
--
作者：
Brown JN;Kohler JJ;Coberley CR;Sleasman JW;Goodenow MM
巨噬细胞提供先天性免疫和适应性免疫之间的接口，是人类免疫缺陷病毒 1 型 (HIV-1) 的重要长寿命储存库。 HIV-1 感染协调调节巨噬细胞中参与调节信号转导级联和免疫反应的多个遗传网络。为了评估复杂的相互关联的过程并整合激活的信号网络的综合视图，系统生物学策略被应用于人类原代巨噬细胞在 HIV-1 感染过程中的基因组和蛋白质组反应。在没有细胞增殖的情况下，巨噬细胞对 HIV-1 的反应，包括细胞周期、钙、细胞凋亡、丝裂原激活蛋白激酶 (MAPK) 和细胞因子/趋化因子，受到暂时调节。相比之下，尽管 TLR 3、4、7 和 8 在巨噬细胞中表达并响应配体刺激，但 Toll 样受体 (TLR) 通路仍未受到 HIV-1 的改变。 HIV-1 无法激活 IRAK-1 或 IRF-3 的磷酸化，无法调节细胞内干扰素刺激基因 Mx1 的蛋白水平，也无法刺激 TNF、IL-1β 或 IL-6 的分泌。 TLR 以外的途径的激活不足以通过分子中枢的串扰机制刺激 TLR 反应典型的促炎细胞因子的产生。 HIV-1 使巨噬细胞对 TLR 配体反应敏感，病毒启动的程度与病毒复制有关。 HIV-1 诱导启动的促炎状态 M1HIV，从而增加巨噬细胞对 TLR 配体的反应性。 HIV-1可能被动地逃避模式识别，主动抑制或抑制识别和信号传导，或者需要巨噬细胞和其他细胞（例如淋巴细胞或内皮细胞）之间的动态相互作用。 HIV-1逃避TLR识别并同时启动巨噬细胞可能代表病毒生存的策略，有助于免疫发病机制，并为治疗方法提供重要靶点。
Macrophages provide an interface between innate and adaptive immunity and are important long-lived reservoirs for Human Immunodeficiency Virus Type-1 (HIV-1). Multiple genetic networks involved in regulating signal transduction cascades and immune responses in macrophages are coordinately modulated by HIV-1 infection. To evaluate complex interrelated processes and to assemble an integrated view of activated signaling networks, a systems biology strategy was applied to genomic and proteomic responses by primary human macrophages over the course of HIV-1 infection. Macrophage responses, including cell cycle, calcium, apoptosis, mitogen-activated protein kinases (MAPK), and cytokines/chemokines, to HIV-1 were temporally regulated, in the absence of cell proliferation. In contrast, Toll-like receptor (TLR) pathways remained unaltered by HIV-1, although TLRs 3, 4, 7, and 8 were expressed and responded to ligand stimulation in macrophages. HIV-1 failed to activate phosphorylation of IRAK-1 or IRF-3, modulate intracellular protein levels of Mx1, an interferon-stimulated gene, or stimulate secretion of TNF, IL-1β, or IL-6. Activation of pathways other than TLR was inadequate to stimulate, via cross-talk mechanisms through molecular hubs, the production of proinflammatory cytokines typical of a TLR response. HIV-1 sensitized macrophage responses to TLR ligands, and the magnitude of viral priming was related to virus replication. HIV-1 induced a primed, proinflammatory state, M1HIV, which increased the responsiveness of macrophages to TLR ligands. HIV-1 might passively evade pattern recognition, actively inhibit or suppress recognition and signaling, or require dynamic interactions between macrophages and other cells, such as lymphocytes or endothelial cells. HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches.
登录
查看更多内容
影响因子：
15.9
作者：
Beignon, AS;McKenna, K;Bhardwaj, N
通讯作者：
Bhardwaj, N
影响因子：
64.8
作者：
Geleziunas, R;Xu, WD;Greene, WC
通讯作者：
Greene, WC
影响因子：
5.4
作者：
Badou, A;Bennasser, Y;Bahraoui, E
通讯作者：
Bahraoui, E
人类免疫缺陷病毒对重组刺激因子1处理的单核细胞的有效分离和传播。
影响因子：
15.3
作者：
GENDELMAN, HE;ORENSTEIN, JM;MARTIN, MA;FERRUA, C;MITRA, R;PHIPPS, T;WAHL, LA;LANE, HC;FAUCI, AS;BURKE, DS;SKILLMAN, D;MELTZER, MS
通讯作者：
MELTZER, MS
影响因子：
3.2
作者：
Fischer-Smith, T;Croul, S;Rappaport, J
通讯作者：
Rappaport, J