The M3 muscarinic receptor is required for optimal adaptive immunity to helminth and bacterial infection.
The M3 muscarinic receptor is required for optimal adaptive immunity to helminth and bacterial infection.
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DOI：
10.1371/journal.ppat.1004636
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发表时间：
2015-01
期刊：
影响因子：
6.7
通讯作者：
Horsnell WG
中科院分区：
文献类型：
--
作者：
Darby M;Schnoeller C;Vira A;Culley FJ;Bobat S;Logan E;Kirstein F;Wess J;Cunningham AF;Brombacher F;Selkirk ME;Horsnell WG
先天免疫是通过烟碱乙酰胆碱受体的胆碱能信号传导调节的。我们在这里表明，通过M3毒蕈碱乙酰胆碱受体（M3R）的信号传导在对巴西尼波圆线虫和肠炎沙门氏菌血清型鼠伤寒沙门氏菌的适应性免疫中起重要作用，因为M3R-/-小鼠在解决两种病原体感染的能力受损。M3R-/-小鼠的CD4 T细胞活化和细胞因子产生降低。M3R-/-小鼠对巴西孢子虫继发感染的免疫功能严重受损，细胞因子反应降低，肺中产生黏液的杯状细胞和选择性活化的巨噬细胞数量减少。用毒蕈碱激动剂刺激感染巴西芽孢杆菌和鼠伤寒沙门氏菌的完整BALB/c小鼠的体外淋巴细胞，分别导致IL-13和IFN-γ的产生增加，而这一过程被一种m3r选择性拮抗剂阻断。因此，我们的数据表明，通过M3R的胆碱能信号传导对于优化Th1和Th2对感染的适应性免疫至关重要。最近的数据表明，乙酰胆碱（ACh）是一种调节多种生理功能的神经递质，也影响免疫系统，淋巴细胞具有合成和释放ACh的能力，控制局部先天免疫反应和抑制炎症。然而，到目前为止，几乎没有证据表明乙酰胆碱影响适应性免疫，其特征是淋巴细胞的激活和效应功能。我们在这里表明，在对两种不同病原体的免疫反应中，乙酰胆碱信号通过毒蕈碱受体和M3受体亚型特异性地传递，导致“辅助”T淋巴细胞的激活和细胞因子的产生增强，从而保护宿主免受感染。
Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R-/- mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R-/- mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R-/- mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-γ respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection. Recent data indicate that acetylcholine (ACh), a neurotransmitter which regulates a variety of physiological functions, also influences the immune system, and that lymphocytes have the capacity to synthesise and release ACh, controlling local innate immune responses and suppressing inflammation. Thus far however there has been little evidence to suggest that ACh influences adaptive immunity, characterised by activation and effector functions of lymphocytes. We show here that during the immune response to two different pathogens, ACh signals through muscarinic receptors, and the M3 receptor subtype specifically, resulting in enhanced activation and cytokine production by ‘helper’ T lymphocytes which protect the host against infection.
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影响因子：
3.5
作者：
Mitsuya, M;Mase, T;Tomimoto, K
通讯作者：
Tomimoto, K
DOI：
10.1073/pnas.1221655110
发表时间：
2013-01-22
影响因子：
11.1
作者：
Reardon, Colin;Duncan, Gordon S.;Mak, Tak W.
通讯作者：
Mak, Tak W.
影响因子：
8
作者：
Horsnell, W. G. C.;Vira, A.;Brombacher, F.
通讯作者：
Brombacher, F.
DOI：
10.1165/rcmb.2013-0220oc
发表时间：
2014-04-01
影响因子：
6.4
作者：
Kistemaker, Loes E. M.;Bos, Sophie T.;Gosens, Reinoud
通讯作者：
Gosens, Reinoud
影响因子：
2.7
作者：
Ebihara, T;Guo, FF;Saffen, D
通讯作者：
Saffen, D