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Neurturin regulates the lung-resident macrophage inflammatory response to viral infection.
Life Science Alliance ( IF 4.4 ) Pub Date : 2020-10-05 , DOI: 10.26508/lsa.202000780
Emma Connolly 1, 2 , David J Morgan 1, 2 , Miriam Franklin 1, 2 , Angela Simpson 3 , Rajesh Shah 4 , Oliver J Brand 1, 2 , Christopher P Jagger 1, 2 , Joshua Casulli 1, 2 , Karishma Mohamed 1, 2 , Aleksander M Grabiec 2 , Tracy Hussell 2, 5
Affiliation  

Lung-resident macrophages are crucial to the maintenance of health and in the defence against lower respiratory tract infections. Macrophages adapt to local environmental cues that drive their appropriate function; however, this is often dysregulated in many inflammatory lung pathologies. In mucosal tissues, neuro-immune interactions enable quick and efficient inflammatory responses to pathogenic threats. Although a number of factors that influence the antimicrobial response of lung macrophages are known, the role of neuronal factors is less well understood. Here, we show an intricate circuit involving the neurotrophic factor, neurturin (NRTN) on human lung macrophages that dampens pro-inflammatory cytokine release and modulates the type of matrix metalloproteinases produced in response to viral stimuli. This circuit involves type 1 interferon-induced up-regulation of RET that when combined with the glial cell line-derived neurotrophic factor (GDNF) receptor α2 (GFRα2) allows binding to epithelial-derived NRTN. Our research highlights a non-neuronal immunomodulatory role for NRTN and a novel process leading to a specific antimicrobial immune response by human lung-resident macrophages.

中文翻译:

Neurturin 调节肺部巨噬细胞对病毒感染的炎症反应。

肺部巨噬细胞对于维持健康和防御下呼吸道感染至关重要。巨噬细胞适应驱动其适当功能的局部环境线索;然而,这在许多炎症性肺病症中经常失调。在粘膜组织中,神经免疫相互作用能够对致病威胁做出快速有效的炎症反应。尽管影响肺部巨噬细胞抗菌反应的许多因素是已知的,但神经元因素的作用却鲜为人知。在这里,我们展示了一个复杂的回路,涉及人肺巨噬细胞上的神经营养因子神经营养因子 (NRTN),它抑制促炎细胞因子的释放并调节响应病毒刺激而产生的基质金属蛋白酶的类型。该回路涉及 1 型干扰素诱导的 RET 上调,当与神经胶质细胞系衍生的神经营养因子 (GDNF) 受体 α2 (GFRα2) 结合时,允许与上皮衍生的 NRTN 结合。我们的研究强调了 NRTN 的非神经元免疫调节作用,以及导致人类肺部巨噬细胞产生特异性抗菌免疫反应的新过程。
更新日期:2020-10-08
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