Duquesne University, School of Pharmacy and the Graduate School of Pharmaceutical Sciences, Pittsburgh, PA 15282, United States.
Duquesne University, School of Pharmacy and the Graduate School of Pharmaceutical Sciences, Pittsburgh, PA 15282, United States.
J Neuroimmunol. 2018 Mar 15;316:80-97. doi: 10.1016/j.jneuroim.2017.12.018. Epub 2017 Dec 28.
Neonates are highly susceptible to viral infections in the periphery, potentially due to deviant cytokine responses. Here, we investigated the role of interferon-gamma (IFNγ), a key anti-viral in the neonatal brain. We found that (i) IFNγ, which is critical for viral control and survival in adults, delays mortality in neonates, (ii) IFNγ limits infiltration of macrophages, neutrophils, and T cells in the neonatal brain, (iii) neonates and adults differentially express pathogen recognition receptors and Type I interferons in response to the infection, (iv) both neonates and adults express IFNγ and other Th1-related factors, but expression of many cytokines/chemokines and IFNγ-responsive genes is age-dependent, and (v) administration of IFNγ extends survival and reduces CD4 T cell infiltration in the neonatal brain. Our findings suggest age-dependent expression of cytokine/chemokine profiles in the brain and distinct dynamic interplays between lymphocyte populations and cytokines/chemokines in MV-infected neonates.
新生儿对外周的病毒感染非常敏感，这可能是由于细胞因子反应异常所致。在这里，我们研究了干扰素-γ (IFNγ) 的作用，IFNγ 是新生儿大脑中一种关键的抗病毒物质。我们发现：（i）IFNγ 对成人控制和生存至关重要，但它会延迟新生儿的死亡率；（ii）IFNγ 限制了巨噬细胞、中性粒细胞和 T 细胞在新生儿大脑中的浸润；（iii）新生儿和成人对感染的病原体识别受体和 I 型干扰素的表达不同；（iv）新生儿和成人都表达 IFNγ 和其他 Th1 相关因子，但许多细胞因子/趋化因子和 IFNγ 反应基因的表达具有年龄依赖性；（v）IFNγ 的给药可延长存活时间并减少 MV 感染新生儿大脑中的 CD4 T 细胞浸润。我们的研究结果表明，大脑中细胞因子/趋化因子谱的表达具有年龄依赖性，并且在 MV 感染的新生儿中，淋巴细胞群和细胞因子/趋化因子之间存在明显的动态相互作用。
