Johnson Hannah J, Kochanowsky Joshua A, Chandrasekaran Sambamurthy, Hunter Christopher A, Beiting Daniel P, Koshy Anita A
Neuroscience Graduate Interdisciplinary Program, University of Arizona, Tucson, Arizona, USA.
BIO5 Institute, University of Arizona, Tucson, Arizona, USA.
mSphere. 2025 Jun 25;10(6):e0021625. doi: 10.1128/msphere.00216-25. Epub 2025 May 30.
A select group of pathogens infects neurons in the brain. Prior dogma held that neurons were "defenseless" against infecting microbes, but many studies suggest that neurons can mount anti-microbial defenses. However, a knowledge gap in understanding how neurons respond and to different classes of microorganisms remains. To address this gap, we compared a transcriptional data set derived from primary neuron cultures (PNCs) infected with the neurotropic intracellular parasite with a data set derived from neurons injected with protein . These curated responses were then compared to the transcriptional responses of PNCs infected with the single-stranded RNA viruses, West Nile virus or Zika virus. These analyses highlighted a conserved response to infection associated with chemokines () and cytokines (interferon signaling). However, had diminished IFN-α signaling compared to the viral data sets and was uniquely associated with a decrease in neuron-specific genes (, , ). These data underscore that neurons participate in infection-induced neuroinflammation and illustrate that neurons possess both pathogen-specific and pathogen-conserved responses.IMPORTANCEThough neurons are commonly the target of pathogens that infect the central nervous system (CNS), few data sets assess the neuronal response to infection. This paucity of data is likely because neurons are perceived to have diminished immune capabilities. However, to understand the role of neurons in neuroinflammation and their immune capabilities, their responses must be investigated. Here, we analyzed publicly accessible, neuron-specific data sets to compare neuron responses to a eukaryotic pathogen vs two Orthoflaviviruses. A better understanding of neuron responses to different infections will allow us to develop methods for inhibiting pathways that lead to neuron dysfunction, enhancing those that limit pathogen survival, and mitigating infection-induced damage to the CNS.
一组特定的病原体感染大脑中的神经元。先前的教条认为神经元对感染微生物“毫无防御能力”，但许多研究表明神经元可以启动抗菌防御。然而，在理解神经元如何对不同种类的微生物作出反应方面仍存在知识空白。为了填补这一空白，我们将源自感染嗜神经性细胞内寄生虫的原代神经元培养物（PNCs）的转录数据集与源自注射了蛋白质的神经元的数据集进行了比较。然后将这些精心整理的反应与感染单链RNA病毒西尼罗河病毒或寨卡病毒的PNCs的转录反应进行比较。这些分析突出了与趋化因子（）和细胞因子（干扰素信号传导）相关的对感染的保守反应。然而，与病毒数据集相比，其干扰素-α信号传导减弱，并且与神经元特异性基因（、、）的减少独特相关。这些数据强调神经元参与感染诱导的神经炎症，并表明神经元具有病原体特异性和病原体保守反应。重要性尽管神经元通常是感染中枢神经系统（CNS）的病原体的靶标，但很少有数据集评估神经元对感染的反应。数据匮乏可能是因为人们认为神经元的免疫能力减弱。然而，为了了解神经元在神经炎症中的作用及其免疫能力，必须研究它们的反应。在这里，我们分析了可公开获取的、神经元特异性的数据集，以比较神经元对真核病原体与两种黄病毒属病毒的反应。更好地理解神经元对不同感染的反应将使我们能够开发方法来抑制导致神经元功能障碍的途径，增强限制病原体存活的途径，并减轻感染对中枢神经系统造成的损害。
