Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough.

Autor:	Ruhl CR; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Pasko BL; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Khan HS; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Kindt LM; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Stamm CE; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Franco LH; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Hsia CC; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Zhou M; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Davis CR; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Qin T; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Gautron L; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Center for Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Burton MD; School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA., Mejia GL; School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA., Naik DK; School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA., Dussor G; School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA., Price TJ; School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA., Shiloh MU; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: michael.shiloh@utsouthwestern.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2020 Apr 16; Vol. 181 (2), pp. 293-305.e11. Date of Electronic Publication: 2020 Mar 05.
DOI:	10.1016/j.cell.2020.02.026
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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