Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea

Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea
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DOI:
10.1128/jvi.70.2.898-904.1996
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发表时间:
1996-02-01
影响因子:
5.4
通讯作者:
Lausch, RN
Lausch, RN
中科院分区:
医学2区
文献类型:
--
作者:
Tumpey, TM;Chen, SH;Lausch, RN

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单纯疱疹病毒1型(HSV-1)感染小鼠角膜可引起中性粒细胞迅速渗入。我们调查了这些细胞是否会影响病毒复制。用单抗(MAb)RB6-8C5治疗的BALB/c小鼠血液、脾和角膜中性粒细胞严重耗尽。在这些动物中,在感染后3天,眼睛中的病毒滴度显著高于免疫球蛋白G处理的对照组。到第9天,在对照组中不再检测到病毒,而在中性粒细胞耗竭的宿主中仍存在10(3)至10(6)pfu滴度。此外,病毒更容易传播到单抗RB6-8C5治疗的动物的皮肤和大脑,使他们更容易受到单纯疱疹病毒L诱导的眼睑炎和脑炎的影响。只有25%的试验组动物存活下来,而对照组的所有动物都存活了下来。虽然单抗RB6-8C5治疗不改变CD4(+)T细胞、B细胞、自然杀伤细胞或巨噬细胞的数量,但CD8(+)T细胞数量部分减少。因此,这些实验在缺乏CD8(+)T细胞的严重联合免疫缺陷小鼠身上重复进行。同样,病毒生长在单抗RB6-8C5处理的宿主的眼睛、三叉神经节和大脑中被发现显著增加。这些结果有力地表明,在免疫活性和免疫缺陷小鼠中,中性粒细胞在帮助控制角膜感染后HSV-1的复制和传播方面发挥了重要作用。
Herpes simplex virus type 1 (HSV-1) infection of the murine cornea induces the rapid infiltration of neutrophils. We investigated whether these cells could influence virus replication. BALB/c mice treated with monoclonal antibody (MAb) RB6-8C5 experienced a profound depletion of neutrophils in the bloodstream, spleen, and cornea. In these animals, virus titers in the eye were significantly higher than those in the immunoglobulin G-treated controls at 3 days postinfection. By day 9, virus was no longer detectable in the controls, whereas titers of 10(3) to 10(6) PFU were still present in the neutrophil-depleted hosts. Furthermore, virus spread more readily to the skin and brains of MAb RB6-8C5-treated animals, rendering them significantly more susceptible to HSV l-induced blepharitis and encephalitis. Only 25% of the treated animals survived, whereas all of the controls lived. Although MAb RB6-8C5 treatment did not alter the CD4(+) T-cell, B-cell, natural killer cell, or macrophage populations, the CD8(+) T-cell population was partially reduced. Therefore, the experiments were repeated in severe combined immunodeficiency mice, which lack CD8(+) T cells. Again virus growth was found to be significantly elevated in the eyes, trigeminal ganglia, and brains of the MAb RB6-8C5-treated hosts. These results strongly indicate that in both immunocompetent and immunodeficient mice, neutrophils play a significant role in helping to control the replication and spread of HSV-1 after corneal infection.