Innate Immune Memory: Implications for Microglial Function and Neuroprogression.
Innate Immune Memory: Implications for Microglial Function and Neuroprogression.
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DOI：
10.1159/000470808
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Zunszain, Patricia
中科院分区：
文献类型：
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作者：
Salam, Alex P;Pariante, Carmine M;Zunszain, Patricia
免疫刺激性损伤，如应激和感染，是几种以神经进展为特征的神经精神疾病发展的危险因素。大脑中的炎性和神经毒性分子可导致神经发生、神经元兴奋性、突触传递、突触可塑性和神经元存活的中断--这些变化是神经进展的特征。我们借鉴了免疫学文献中的最新发现，即外周固有免疫细胞能够保持对感染性侮辱的长期记忆，并显示出长期上调的促炎功能，以应对反复的感染性侮辱--这一概念被称为“先天性免疫记忆”。反过来，我们假设小胶质细胞--大脑的固有免疫细胞--也能够对感染性和非感染性侮辱保持长期记忆，包括压力。小胶质细胞能够产生多种促炎、神经毒性细胞因子和趋化因子。因此，由于对免疫刺激性损伤的记忆导致小胶质细胞致炎功能的持续上调，可能导致神经精神疾病的持续和进行性炎症，并成为神经进展的重要驱动因素。
Immunostimulatory insults such as stress and infection are risk factors for the development of several neuropsychiatric disorders characterized by neuroprogression. Inflammatory and neurotoxic molecules in the brain can cause disruptions in neurogenesis, neuronal excitability, synaptic transmission, synaptic plasticity, and neuronal survival - changes that characterize neuroprogression. We draw on recent findings in the immunology literature that peripheral innate immune cells are capable of retaining long-term memory of infectious insults and displaying long-lasting upregulated proinflammatory function in response to repeated infectious insults - a concept known as "innate immune memory." In turn, we hypothesize that microglia, the resident innate immune cells of the brain, are also capable of retaining long-term memory of infectious and noninfectious insults, including stress. Microglia are capable of producing a variety of proinflammatory neurotoxic cytokines and chemokines. Persistent upregulation of microglial proinflammatory function as a result of memory for immunostimulatory insults may therefore contribute to persistent and progressive inflammation in neuropsychiatric illnesses and be an important driver of neuroprogression.