Increased phagocytosis in the presence of enhanced M2-like macrophage responses correlates with increased primary and latent HSV-1 infection.
Increased phagocytosis in the presence of enhanced M2-like macrophage responses correlates with increased primary and latent HSV-1 infection.
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DOI：
10.1371/journal.ppat.1008971
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发表时间：
2020-10
期刊：
影响因子：
6.7
通讯作者：
Ghiasi H
中科院分区：
文献类型：
--
作者：
Jaggi U;Yang M;Matundan HH;Hirose S;Shah PK;Sharifi BG;Ghiasi H
在HSV-1感染后，巨噬细胞早期浸润到角膜中，在那里它们在HSV-1感染中起重要作用。大分子化合物根据其活化分为M1或M2组。M1巨噬细胞是促炎的，而M2巨噬细胞是抗炎的。巨噬细胞表型可以在体外和体内用特异性细胞因子治疗后在M1或M2之间转变。在这项研究中，我们使用缺乏M2（M2-/-）或过表达M2（M2-OE）巨噬细胞的小鼠观察了M2巨噬细胞对HSV-1感染性的影响。虽然存在或不存在M2巨噬细胞对眼部疾病没有影响，但我们发现M2巨噬细胞的过度表达与吞噬作用增加、原发性病毒复制增加、潜伏期增加以及促炎和抗炎细胞因子表达增加相关。相反，在感染后缺乏M2巨噬细胞的小鼠中，吞噬作用、复制、潜伏期和细胞因子表达与野生型小鼠相似。我们的研究结果表明，增强的M2反应导致更高的吞噬作用，影响原发性和潜伏性感染，但不重新激活。巨噬细胞是眼部感染小鼠角膜的主要浸润细胞之一，可能有助于疾病和保护。与TH 1/TH 2 T细胞类似，巨噬细胞也分为M1/M2亚型。然而，很少有人知道的作用，如果有的话，M1/M2巨噬细胞在HSV-1的原发性和潜伏性感染。在这里，我们通过产生M2-/-小鼠以及过表达M2巨噬细胞的条件性转基因小鼠来研究M1/M2巨噬细胞在HSV-1潜伏再激活中的作用。我们发现，M2巨噬细胞的高表达与较高的吞噬作用、较高的原代病毒复制和潜伏期以及较高的IL-4和IFN-γ表达相关，而与野生型小鼠相比，M2巨噬细胞的缺失并没有显著改变HSV-1的感染性。因此，维持M1/M2巨噬细胞表型的平衡比例可能是控制原发性和潜伏性感染的有效方法。
After HSV-1 infection, macrophages infiltrate early into the cornea, where they play an important role in HSV-1 infection. Macrophages are divided into M1 or M2 groups based on their activation. M1 macrophages are pro-inflammatory, while M2 macrophages are anti-inflammatory. Macrophage phenotypes can shift between M1 or M2 in vitro and in vivo following treatment with specific cytokines. In this study we looked at the effect of M2 macrophages on HSV-1 infectivity using mice either lacking M2 (M2-/-) or overexpressing M2 (M2-OE) macrophages. While presence or absence of M2 macrophages had no effect on eye disease, we found that over expression of M2 macrophages was associated with increased phagocytosis, increased primary virus replication, increased latency, and increased expression of pro- and anti-inflammatory cytokines. In contrast, in mice lacking M2 macrophages following infection phagocytosis, replication, latency, and cytokine expression were similar to wild type mice. Our results suggest that enhanced M2 responses lead to higher phagocytosis, which affected both primary and latent infection but not reactivation. Macrophages are one of the major infiltrates into the cornea of ocularly infected mice and may contribute to both disease and protection. Similar to TH1/TH2 T cells, macrophages also are divided into M1/M2 subtypes. However, very little is known about the role, if any, that M1/M2 macrophages play in HSV-1 primary and latent infection. Here we investigated the role of M1/M2 macrophages in HSV-1 latency-reactivation by generating M2-/- mice as well as conditional transgenic mice that overexpress M2 macrophages. We found that higher expression of M2 macrophages correlated with higher phagocytosis, higher primary virus replication and latency, and higher IL-4 and IFN-γ expression, while the absence of M2 macrophages did not significantly alter HSV-1 infectivity compared with wild type mice. Thus, maintaining a balanced proportion of M1/M2 macrophage phenotype may be an effective way to control both primary and latent infection.
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