Cell
Volume 181, Issue 2, 16 April 2020, Pages 293-305.e11
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Article
Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough

https://doi.org/10.1016/j.cell.2020.02.026Get rights and content
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Highlights

  • An Mtb organic extract activates nociceptive neurons and induces cough in guinea pigs

  • Mtb sulfolipid-1 is necessary and sufficient to trigger neuronal activation and cough

  • Guinea pigs infected with an SL-1-deficient Mtb mutant do not cough

Summary

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.

Keywords

mycobacteria
tuberculosis
cough
glycolipid
sulfolipid
host-pathogen
mucosal immunology
neuro-immune
nociceptor

Cited by (0)

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Present address: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte 30270-901, Brazil

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