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Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough.
Cell ( IF 64.5 ) Pub Date : 2020-03-05 , DOI: 10.1016/j.cell.2020.02.026
Cody R Ruhl 1 , Breanna L Pasko 1 , Haaris S Khan 1 , Lexy M Kindt 1 , Chelsea E Stamm 1 , Luis H Franco 1 , Connie C Hsia 1 , Min Zhou 2 , Colton R Davis 2 , Tian Qin 2 , Laurent Gautron 3 , Michael D Burton 4 , Galo L Mejia 4 , Dhananjay K Naik 4 , Gregory Dussor 4 , Theodore J Price 4 , Michael U Shiloh 5
Affiliation  

Pulmonary tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), manifests with a persistent cough as both a primary symptom and mechanism of transmission. The cough reflex can be triggered by nociceptive neurons innervating the lungs, and some bacteria produce neuron-targeting molecules. However, how pulmonary Mtb infection causes cough remains undefined, and whether Mtb produces a neuron-activating, cough-inducing molecule is unknown. Here, we show that an Mtb organic extract activates nociceptive neurons in vitro and identify the Mtb glycolipid sulfolipid-1 (SL-1) as the nociceptive molecule. Mtb organic extracts from mutants lacking SL-1 synthesis cannot activate neurons in vitro or induce cough in a guinea pig model. Finally, Mtb-infected guinea pigs cough in a manner dependent on SL-1 synthesis. Thus, we demonstrate a heretofore unknown molecular mechanism for cough induction by a virulent human pathogen via its production of a complex lipid.

中文翻译:

结核分枝杆菌Sulfolipid-1激活伤害性神经元并诱发咳嗽。

肺结核是一种由结核分枝杆菌(Mtb)引起的疾病,表现为持续咳嗽,这是主要症状和传播机制。咳嗽反射可由神经支配肺部的伤害性神经元触发,某些细菌产生靶向神经元的分子。但是,肺部Mtb感染如何引起咳嗽仍不确定,并且Mtb是否产生神经元激活的咳嗽诱导分子尚不清楚。在这里,我们显示Mtb有机提取物在体外激活伤害感受性神经元,并将Mtb糖脂硫脂1(SL-1)鉴定为伤害感受性分子。来自缺乏SL-1合成的突变体的Mtb有机提取物不能在豚鼠模型中体外激活神经元或诱发咳嗽。最后,Mtb感染的豚鼠以依赖SL-1合成的方式咳嗽。从而,
更新日期:2020-04-20
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