Depletion of macrophages in mice results in higher dengue virus titers and highlights the role of macrophages for virus control
Depletion of macrophages in mice results in higher dengue virus titers and highlights the role of macrophages for virus control
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DOI：
10.1002/eji.200939389
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发表时间：
2009-10-01
影响因子：
5.4
通讯作者：
Schul, Wouter
中科院分区：
文献类型：
--
作者：
Fink, Katja;Ng, Cedrig;Schul, Wouter
单核细胞和巨噬细胞是登革热感染的靶细胞。除了它们在病毒复制中可能具有的作用外，活化的单核细胞/巨噬细胞产生的细胞因子可能对登革热病理至关重要。为了研究单核细胞和巨噬细胞在体内对病毒复制的作用，我们在登革热感染前用氯膦酸盐脂质体清除干扰素 -αβγR基因敲除小鼠的单核细胞和巨噬细胞。尽管在没有巨噬细胞的情况下，引流淋巴结中最初恢复的病毒较少，但单核细胞/巨噬细胞的清除最终导致全身病毒滴度升高了10倍。在病毒血症得到控制之前，随着病毒滴度的增加，观察到大量CD11b(+)CD11c(低)Ly6C(低)单核细胞浸润到感染器官。在局部感染之前或之后清除血液中的单核细胞对病毒滴度没有影响，这表明单核细胞并非作为“病毒穿梭体”是必需的。我们的数据提供了证据，表明全身性病毒血症的建立与感染部位的组织巨噬细胞和血液单核细胞无关。相反，我们证明了单核细胞/巨噬细胞对登革热病毒控制的重要性。
Monocytes and macrophages are target cells for dengue infection. Besides their potential role for virus replication, activated monocytes/macrophages produce cytokines that may be critical for dengue pathology. To study the in vivo role of monocytes and macrophages for virus replication, we depleted monocytes and macrophages in IFN-alpha beta gamma R knockout mice with clodronate liposomes before dengue infection. Although less virus was first recovered in the draining LN in the absence of macrophages, monocyte/macrophage depletion eventually resulted in a ten-fold higher systemic viral titer. A massive infiltration of CD11b(+)CD11c(low)Ly6C(low) monocytes into infected organs was observed in parallel with increasing virus titers before viremia. was controlled. Depletion of monocytes in the blood before or after local infection had no impact on virus titers, suggesting that monocytes are not required as "virus-shuttles". Our data provide evidence that systemic viremia is established independently of tissue macrophages present at the site of infection and blood monocytes. Instead, we demonstrate the importance of monocytes/macrophages for the control of dengue virus.