约翰霍普金斯大学Nicole Baumgarth团队揭示了B细胞通过神经递质乙酰胆碱调节肺部抗病毒炎症反应。该项研究成果发表在2025年4月22日出版的《自然—免疫学》上。

在目前的研究中，研究组发现产生乙酰胆碱（ACh）的B细胞是这种早期调节剂。B细胞是呼吸道中最常见的产生乙酰胆碱转移酶(ChAT)-绿色荧光蛋白（GFP）报告的白细胞群，在感染甲型流感病毒之前和之后。在B细胞中缺乏ChAT的小鼠，使其产生ACh的能力丧失（ChatBKO），但在T细胞中没有缺乏ChAT，显著、选择性和直接抑制了间质而非肺泡巨噬细胞的α7-烟酸-ACh受体表达及其分泌肿瘤坏死因子（TNF）的能力，同时在感染后1d更好地控制病毒复制。相反，通过单克隆抗体治疗阻断TNF会增加当时的病毒载量。感染第10天，尽管病毒载量和病毒清除相似，ChatBKO小鼠表现出局部和全身炎症增加，肺上皮修复迹象减少。因此，B细胞是控制病毒感染后肺组织损伤的直接早期调节级联反应的关键参与者，以增强早期病毒复制为代价，将平衡转向减少炎症。

据悉，先天免疫防御的快速启动对于感染宿主病毒复制的早期控制至关重要，但它也可能导致不可逆的组织损伤，特别是在呼吸道。在控制感染的同时，还存在一些敏感的调节因子来调节炎症。

附：英文原文

Title: B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine

Author: Cembellin-Prieto, Antonio, Luo, Zheng, Kulaga, Heather, Baumgarth, Nicole

Issue&Volume: 2025-04-22

Abstract: The rapid onset of innate immune defenses is critical for early control of viral replication in an infected host and yet it can also lead to irreversible tissue damage, especially in the respiratory tract. Sensitive regulators must exist that modulate inflammation, while controlling the infection. In the present study, we identified acetylcholine (ACh)-producing B cells as such early regulators. B cells are the most prevalent ACh-producing leukocyte population in the respiratory tract demonstrated with choline acetyltransferase (ChAT)-green fluorescent protein (GFP) reporter mice, both before and after infection with influenza A virus. Mice lacking ChAT in B cells, disabling their ability to generate ACh (ChatBKO), but not those lacking ChAT in T cells, significantly, selectively and directly suppressed α7-nicotinic-ACh receptor-expressing interstitial, but not alveolar, macrophage activation and their ability to secrete tumor necrosis factor (TNF), while better controlling virus replication at 1d postinfection. Conversely, TNF blockade via monoclonal antibody treatment increased viral loads at that time. By day 10 of infection, ChatBKO mice showed increased local and systemic inflammation and reduced signs of lung epithelial repair despite similar viral loads and viral clearance. Thus, B cells are key participants of an immediate early regulatory cascade that controls lung tissue damage after viral infection, shifting the balance toward reduced inflammation at the cost of enhanced early viral replication.

DOI: 10.1038/s41590-025-02124-8

Source: https://www.nature.com/articles/s41590-025-02124-8