In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.

In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.
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DOI:
10.1038/s41598-017-17765-5
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发表时间:
2018-01-08
期刊:
影响因子:
4.6
通讯作者:
Vasconcelos PFC
Vasconcelos PFC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Azevedo RSS;de Sousa JR;Araujo MTF;Martins Filho AJ;de Alcantara BN;Araujo FMC;Queiroz MGL;Cruz ACR;Vasconcelos BHB;Chiang JO;Martins LC;Casseb LMN;da Silva EV;Carvalho VL;Vasconcelos BCB;Rodrigues SG;Oliveira CS;Quaresma JAS;Vasconcelos PFC

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寨卡病毒(ZIKV)近期引发了一场大流行疾病,许多孕妇感染寨卡病毒的病例导致了流产、死产、死亡以及包括小头畸形在内的先天性缺陷,现在小头畸形已被提出作为寨卡病毒先天性综合征。本研究旨在调查致命性寨卡小头畸形病例中原位免疫反应特征以及神经元细胞损伤的机制。从15例病例中收集了脑组织样本,其中包括10例小头畸形且寨卡病毒检测呈阳性且预后不良的新生儿,以及5例因其他原因死亡但中枢神经系统(CNS)结构保存完好且黄病毒检测呈阴性的新生儿作为对照。在小头畸形病例中,对三个中枢神经系统区域(脑膜、血管周围间隙和脑实质)的组织样本进行了组织病理学特征分析。所发现的变化主要包括钙化、坏死、噬神经现象、神经胶质增生、小胶质细胞结节以及单核细胞的炎症浸润。新生儿中枢神经系统中针对寨卡病毒的原位免疫反应是复杂的。尽管Th2细胞因子占主导表达,但其他细胞因子如Th1、Th17、Treg、Th9和Th22也在较小程度上参与其中,但仍可能参与寨卡病毒导致的致命性小头畸形病例中神经疾病的免疫致病机制。
Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.
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