Smith Katie J, Gwyer Findlay Emily
Centre for Inflammation Research, University of Edinburgh, 47 Little France Crescent, EH16 4TJ, Edinburgh, UK.
Discov Immunol. 2022 Jul 26;1(1):kyac003. doi: 10.1093/discim/kyac003. eCollection 2022.
Antimicrobial host defence peptides (HDP) are critical for the first line of defence against bacterial, viral, and fungal pathogens. Over the past decade we have become more aware that, in addition to their antimicrobial roles, they also possess the potent immunomodulatory capacity. This includes chemoattracting immune cells, activating dendritic cells and macrophages, and altering T-cell differentiation. Most examinations of their immunomodulatory roles have focused on tissues in which they are very abundant, such as the intestine and the inflamed skin. However, HDP have now been detected in the brain and the spinal cord during a number of conditions. We propose that their presence in the central nervous system (CNS) during homeostasis, infection, and neurodegenerative disease has the potential to contribute to immunosurveillance, alter host responses and skew developing immunity. Here, we review the evidence for HDP expression and function in the CNS in health and disease. We describe how a wide range of HDP are expressed in the CNS of humans, rodents, birds, and fish, suggesting a conserved role in protecting the brain from pathogens, with evidence of production by resident CNS cells. We highlight differences in methodology used and how this may have resulted in the immunomodulatory roles of HDP being overlooked. Finally, we discuss what HDP expression may mean for CNS immune responses.
抗菌宿主防御肽（HDP）是抵御细菌、病毒和真菌病原体的第一道防线的关键组成部分。在过去十年中，我们越来越清楚地认识到，除了抗菌作用外，它们还具有强大的免疫调节能力。这包括趋化免疫细胞、激活树突状细胞和巨噬细胞，以及改变T细胞分化。对其免疫调节作用的大多数研究都集中在它们含量非常丰富的组织，如肠道和炎症皮肤。然而，现在已经在多种情况下在大脑和脊髓中检测到了HDP。我们认为，在稳态、感染和神经退行性疾病期间，它们在中枢神经系统（CNS）中的存在有可能促进免疫监视、改变宿主反应并影响发育中的免疫。在此，我们综述了HDP在健康和疾病状态下在中枢神经系统中的表达和功能的证据。我们描述了多种HDP如何在人类、啮齿动物、鸟类和鱼类的中枢神经系统中表达，这表明它们在保护大脑免受病原体侵害方面具有保守作用，并且有证据表明是由中枢神经系统驻留细胞产生的。我们强调了所使用方法的差异以及这可能如何导致HDP的免疫调节作用被忽视。最后，我们讨论了HDP表达对中枢神经系统免疫反应可能意味着什么。
