Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA.
Department of Biology, Rio Piedras Campus, University of Puerto Rico, San Juan, PR 00931, USA.
Int J Mol Sci. 2023 Oct 29;24(21):15732. doi: 10.3390/ijms242115732.
Macrophages serve as vital defenders, protecting the body by exhibiting remarkable cellular adaptability in response to invading pathogens and various stimuli. These cells express nicotinic acetylcholine receptors, with the α7-nAChR being extensively studied due to its involvement in activating the cholinergic anti-inflammatory pathway. Activation of this pathway plays a crucial role in suppressing macrophages' production of proinflammatory cytokines, thus mitigating excessive inflammation and maintaining host homeostasis. Macrophage polarization, which occurs in response to specific pathogens or insults, is a process that has received limited attention concerning the activation of the cholinergic anti-inflammatory pathway and the contributions of the α7-nAChR in this context. This review aims to present evidence highlighting how the cholinergic constituents in macrophages, led by the α7-nAChR, facilitate the polarization of macrophages towards anti-inflammatory phenotypes. Additionally, we explore the influence of viral infections on macrophage inflammatory phenotypes, taking into account cholinergic mechanisms. We also review the current understanding of macrophage polarization in response to these infections. Finally, we provide insights into the relatively unexplored partial duplication of the α7-nAChR, known as dup α7, which is emerging as a significant factor in macrophage polarization and inflammation scenarios.
巨噬细胞作为重要的防御细胞,通过对入侵病原体和各种刺激表现出显著的细胞适应性来保护身体。这些细胞表达烟碱型乙酰胆碱受体,其中α7-nAChR 因其参与激活胆碱能抗炎途径而被广泛研究。该途径的激活在抑制巨噬细胞产生促炎细胞因子方面起着至关重要的作用,从而减轻过度炎症和维持宿主内稳态。巨噬细胞极化是一种对特定病原体或损伤的反应,关于该途径的激活以及α7-nAChR 在这种情况下的贡献,其相关研究受到了限制。本综述旨在提供证据,强调由α7-nAChR 介导的巨噬细胞中的胆碱能成分如何促进巨噬细胞向抗炎表型的极化。此外,我们探讨了病毒感染对巨噬细胞炎症表型的影响,同时考虑到胆碱能机制。我们还回顾了目前对这些感染中巨噬细胞极化的理解。最后,我们深入探讨了相对未被探索的α7-nAChR 部分重复,即 dup α7,它在巨噬细胞极化和炎症场景中成为一个重要因素。