HIV-1 infection-induced apoptotic microparticles inhibit human DCs via CD44
HIV-1 infection-induced apoptotic microparticles inhibit human DCs via CD44
复制标题
DOI：
10.1172/jci64439
复制
发表时间：
2012-12-01
影响因子：
15.9
通讯作者：
Bhardwaj, Nina
中科院分区：
文献类型：
--
作者：
Frleta, Davor;Ochoa, Carolyn E.;Bhardwaj, Nina
急性HIV-1感染导致免疫失调，导致病毒感染控制不良。DC是控制HIV-1所需的适应性和先天性免疫反应的关键调节因子，我们推测在急性HIV-1感染期间引起的因素可能会阻碍DC功能。我们从健康供体外周血单核细胞中获得未成熟的DC，并用来自未感染对照供体和急性HIV-1感染供体的血浆处理它们。我们发现，来自HIV患者的血浆特异性地抑制DC功能。这种抑制是由急性HIV-1感染期间来自垂死细胞的凋亡微粒升高介导的。凋亡微粒通过透明质酸受体CD 44结合并抑制DC。这些数据表明，通过凋亡微粒靶向这种CD 44介导的抑制可能是一种增强DC激活HIV特异性免疫的新策略。
Acute HIV-1 infection results in dysregulated immunity, which contributes to poor control of viral infection. DCs are key regulators of both adaptive and innate immune responses needed for controlling HIV-1, and we surmised that factors elicited during acute HIV-1 infection might impede DC function. We derived immature DCs from healthy donor peripheral blood monocytes and treated them with plasma from uninfected control donors and donors with acute HIV-1 infections. We found that the plasma from patients with HIV specifically inhibited DC function. This suppression was mediated by elevated apoptotic microparticles derived from dying cells during acute HIV-1 infection. Apoptotic microparticles bound to and inhibited DCs through the hyaluronate receptor CD44. These data suggest that targeting this CD44-mediated inhibition by apoptotic microparticles could be a novel strategy to potentiate DC activation of HIV-specific immunity.