Aging and neuroinflammation: Changes in immune cell responses, axon integrity, and motor function in a viral model of progressive multiple sclerosis,Aging Cell

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Aging and neuroinflammation: Changes in immune cell responses, axon integrity, and motor function in a viral model of progressive multiple sclerosis
Aging Cell ( IF 8.0 ) Pub Date : 2021-08-06 , DOI: 10.1111/acel.13440
Leyre Mestre _{1,

2} , Graciela Alonso _{1,

2} , Ana Feliú _{1,

2} , Miriam Mecha _{1,

2} , Carolina Martín ₁ , Luisa M Villar _{2,

3} , Carmen Guaza _{1,

2}

Affiliation

Although aggravated multiple sclerosis (MS) disability has been reported in aged patients, the aging impact on immune cells remodeling within the CNS is not well understood. Here, we investigated the influence of aging on immune cells and the neuroinflammatory and neurodegenerative processes that occur in a well-established viral model of progressive MS. We found an anomalous presence of CD4⁺ T, CD8⁺T, B cells, and cells of myeloid lineage in the CNS of old sham mice whereas a blunted cellular innate and adaptive immune response was observed in Theiler's murine encephalomyelitis virus (TMEV) infected old mice. Microglia and macrophages show opposite CNS viral responses regarding cell counts in the old mice. Furthermore, enhanced expression of Programmed Death-ligand 1 (PD-L1) was found in microglia isolated from old TMEV-infected mice and not in isolated CNS macrophages. Immunocytochemical staining of microglial cells confirms the above differences between young and old mice. Age-related axonal loss integrity in the mouse spinal cord was found in TMEV mice, but a less marked neurodegenerative process was present in old sham mice compared with young sham mice. TMEV and sham old mice also display alterations in innate and adaptive immunity in the spleen compared to the young mice. Our study supports the need of new or adapted pharmacological strategies for MS elderly patients.

中文翻译：

衰老和神经炎症：进行性多发性硬化病毒模型中免疫细胞反应、轴突完整性和运动功能的变化

尽管在老年患者中报告了加重的多发性硬化症 (MS) 残疾，但衰老对 CNS 内免疫细胞重塑的影响尚不清楚。在这里，我们研究了衰老对免疫细胞的影响以及在完善的进行性 MS 病毒模型中发生的神经炎症和神经退行性过程。我们发现异常存在 CD4 ⁺ T、CD8 ⁺T、B 细胞和老假小鼠 CNS 中的髓系细胞，而在 Theiler 鼠脑脊髓炎病毒 (TMEV) 感染的老小鼠中观察到细胞先天和适应性免疫反应迟钝。小胶质细胞和巨噬细胞在老年小鼠的细胞计数方面表现出相反的 CNS 病毒反应。此外，在从感染 TMEV 的老年小鼠分离出的小胶质细胞中发现程序性死亡配体 1 (PD-L1) 的表达增强，而在分离的 CNS 巨噬细胞中则没有。小胶质细胞的免疫细胞化学染色证实了年轻和老年小鼠之间的上述差异。在 TMEV 小鼠中发现了小鼠脊髓中与年龄相关的轴突丧失完整性，但与年轻的假小鼠相比，老假小鼠的神经退行性过程不太明显。与年轻小鼠相比，TMEV 和假老小鼠也表现出脾脏中先天免疫和适应性免疫的改变。我们的研究支持 MS 老年患者需要新的或经过调整的药理学策略。

更新日期：2021-09-15

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