肌巨噬细胞内肾上腺素信号可以限制感染引起的神经元缺失，这一成果由美国洛克菲勒大学Daniel Mucida 和Paul A. Muller研究组合作取得。 2020年1月9日，《细胞》在线发表了这项成果。

研究人员探索了感染诱导的炎症对内在肠相关神经元（iEAN）的影响以及肠道肌巨噬细胞（MM）在这种情况下的功能。使用小鼠肠道感染模型，研究人员观察到长期的胃肠道症状，包括运动性降低和兴奋性iEAN的丧失，这些症状是由Nlrp6-和Casp11依赖的机制所介导，并与感染史相关，其可以通过干扰肠道菌群所缓解。MM通过上调β2-肾上腺素受体（β2 -AR）信号传导的神经保护机制应对官腔感染并通过精氨酸酶1-多胺参与的通路发挥神经元保护作用。这项研究揭示了感染后神经元死亡的机制，并指出组织驻留MM在限制神经元损伤中的作用。

科学家介绍，肠相关神经元（EANs）免疫细胞密切相关，并监测和调节体内肠道功能平衡，包括肠运动性和营养感知。在神经退行性疾病或肠易激综合症等疾病中，神经元与免疫细胞之间的双向相互作用会发生改变。

附：英文原文

Title: Adrenergic Signaling in Muscularis Macrophages Limits Infection-Induced Neuronal Loss

Author: Fanny Matheis, Paul A. Muller, Christina L. Graves, Ilana Gabanyi, Zachary J. Kerner, Diego Costa-Borges, Tomasz Ahrends, Philip Rosenstiel, Daniel Mucida

Issue&Volume: 2020/01/09

Abstract: Enteric-associated neurons (EANs) are closely associated with immune cells and continuouslymonitor and modulate homeostatic intestinal functions, including motility and nutrientsensing. Bidirectional interactions between neuronal and immune cells are alteredduring disease processes such as neurodegeneration or irritable bowel syndrome. Weinvestigated the effects of infection-induced inflammation on intrinsic EANs (iEANs)and the role of intestinal muscularis macrophages (MMs) in this context. Using murine models of enteric infections, weobserved long-term gastrointestinal symptoms, including reduced motility and lossof excitatory iEANs, which was mediated by a Nlrp6- and Casp11-dependent mechanism, depended on infection history, and could be reversed by manipulationof the microbiota. MMs responded to luminal infection by upregulating a neuroprotectiveprogram via β2-adrenergic receptor (β2-AR) signaling and mediated neuronal protection through an arginase 1-polyamine axis.Our results identify a mechanism of neuronal death post-infection and point to a rolefor tissue-resident MMs in limiting neuronal damage.

DOI: 10.1016/j.cell.2019.12.002

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31328-5