Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.
Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection.
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DOI：
10.1371/journal.ppat.1009999
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发表时间：
2021-10
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;Matundan HH;Yu J;Hirose S;Mueller M;Wormley FL Jr;Ghiasi H
眼部HSV-1感染是眼部疾病的主要原因，先天性和获得性免疫在眼部感染相关的保护和病理中发挥作用。以前我们已经表明，M1型巨噬细胞是感染小鼠角膜的主要和最早的浸润。我们还表明，在存在和不存在M2-巨噬细胞的情况下，HSV-1的感染性与野生型（WT）对照小鼠相似。然而，尚不清楚M1巨噬细胞的缺乏是否在HSV-1感染小鼠的保护和疾病中起作用。为了探索M1巨噬细胞在HSV-1感染中的作用，我们使用缺乏M1活化的小鼠（M1-/-小鼠）。我们的研究结果表明，M1-/-小鼠的巨噬细胞在体外比WT小鼠的巨噬细胞更容易受到HSV-1感染。M1-/-小鼠对强毒HSV-1株McKrae的眼部感染高度敏感，而WT小鼠对感染不敏感。此外，M1-/-小鼠眼睛中的病毒滴度高于WT小鼠。将M1巨噬细胞从WT小鼠连续转移到M1-/-小鼠减少了死亡，并挽救了感染小鼠眼中的病毒复制。用无毒HSV-1毒株科斯感染M1-/-小鼠也增加了眼部病毒复制和眼部疾病，但不影响WT对照小鼠中观察到的潜伏期再激活。病毒复制和眼部疾病的严重程度与显著更高的炎症反应相关，导致M1-/-感染小鼠眼中的细胞因子风暴，而WT小鼠中未观察到。因此，我们的研究第一次阐明了M1巨噬细胞在原发性HSV-1感染、眼部疾病和生存中的重要性，但在潜伏期再激活中没有。在血液中循环或存在于不同组织中的巨噬细胞构成抗感染的重要屏障。我们先前表明，M2巨噬细胞的缺乏不会影响HSV-1在体内的感染性。然而，在这项研究中，我们证明了M1巨噬细胞在保护原发性HSV-1复制、死亡和眼病中的重要作用，但在潜伏期再激活中没有。
Ocular HSV-1 infection is a major cause of eye disease and innate and adaptive immunity both play a role in protection and pathology associated with ocular infection. Previously we have shown that M1-type macrophages are the major and earliest infiltrates into the cornea of infected mice. We also showed that HSV-1 infectivity in the presence and absence of M2-macrophages was similar to wild-type (WT) control mice. However, it is not clear whether the absence of M1 macrophages plays a role in protection and disease in HSV-1 infected mice. To explore the role of M1 macrophages in HSV-1 infection, we used mice lacking M1 activation (M1-/- mice). Our results showed that macrophages from M1-/- mice were more susceptible to HSV-1 infection in vitro than were macrophages from WT mice. M1-/- mice were highly susceptible to ocular infection with virulent HSV-1 strain McKrae, while WT mice were refractory to infection. In addition, M1-/- mice had higher virus titers in the eyes than did WT mice. Adoptive transfer of M1 macrophages from WT mice to M1-/- mice reduced death and rescued virus replication in the eyes of infected mice. Infection of M1-/- mice with avirulent HSV-1 strain KOS also increased ocular virus replication and eye disease but did not affect latency-reactivation seen in WT control mice. Severity of virus replication and eye disease correlated with significantly higher inflammatory responses leading to a cytokine storm in the eyes of M1-/- infected mice that was not seen in WT mice. Thus, for the first time, our study illustrates the importance of M1 macrophages specifically in primary HSV-1 infection, eye disease, and survival but not in latency-reactivation. Macrophages circulating in the blood or present in different tissues constitute an important barrier against infection. We previously showed that the absence of M2 macrophages does not impact HSV-1 infectivity in vivo. However, in this study we demonstrated an essential role of M1 macrophages in protection from primary HSV-1 replication, death, and eye disease but not in latency-reactivation.
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影响因子：
16.8
作者：
Appay, V;Rowland-Jones, SL
通讯作者：
Rowland-Jones, SL
影响因子：
2.2
作者：
Abram CL;Roberge GL;Hu Y;Lowell CA
通讯作者：
Lowell CA
影响因子：
5.5
作者：
Ghiasi, H;Hofman, FM;Wechsler, SL
通讯作者：
Wechsler, SL
DOI：
10.1126/science.1258025
发表时间：
2015-01-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Baldridge MT;Nice TJ;McCune BT;Yokoyama CC;Kambal A;Wheadon M;Diamond MS;Ivanova Y;Artyomov M;Virgin HW
通讯作者：
Virgin HW
影响因子：
5.4
作者：
Elliott, G;O'Hare, P
通讯作者：
O'Hare, P