Abstract
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. Mycobacterium tuberculosis produces a glycolipid called sulfolipid-1 (SL-1) that triggers cough by activating nociceptive neurons.
Original language | English (US) |
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Pages (from-to) | 293-305.e11 |
Journal | Cell |
Volume | 181 |
Issue number | 2 |
DOIs | |
State | Published - Apr 16 2020 |
Keywords
- cough
- glycolipid
- host-pathogen
- mucosal immunology
- mycobacteria
- neuro-immune
- nociceptor
- sulfolipid
- tuberculosis
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology