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Hitching a ride on a cough?

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Science Signaling  28 Apr 2020:
Vol. 13, Issue 629, eabc4459
DOI: 10.1126/scisignal.abc4459

A component of M. tuberculosis activates nociceptor neurons to induce coughing.

A person infected with Mycobacterium tuberculosis may spread the bacterium to others by coughing, a reflex that can be triggered by TRPV1-positive nociceptive neurons in response to inflammatory molecules or irritants. Ruhl et al. hypothesized that M. tuberculosis produces a molecule that stimulates nociceptive neurons to induce coughing. The authors showed that guinea pigs, which are a model for M. tuberculosis infection, coughed at the highest frequency at 6 weeks after infection. An organic extract of cultured M. tuberculosis induced coughing in naïve guinea pigs and triggered increases in intracellular Ca2+ in immortalized mouse embryonic dorsal root ganglion (DRG) MED17.11 cells. The organic extract also induced increases in intracellular Ca2+ in mouse nodose/jugular ganglia–derived neurons (which can trigger the cough reflex) and DRG neurons (which relay sensory information to the spinal cord) and in human DRG neurons, although the responses in TRPV1-positive human neurons were not universal. MED17.11 cells produced increases in intracellular Ca2+ in response to purified sulfolipid-1 (SL-1), an abundant glycolipid in the outer membrane and cell wall of M. tuberculosis, but not to organic extracts of bacteria with mutations that disrupted SL-1 synthesis. SL-1 application resulted in increases in intracellular Ca2+ in TRPV1-positive mouse nodose/jugular ganglia–derived and DRG neurons, as well as in human DRG neurons, albeit to a lesser extent. Administration of SL-1 triggered coughing in naïve guinea pigs, but guinea pigs did not cough when infected with bacteria that did not produce SL-1. These results suggest that a component of M. tuberculosis activates nociceptor neurons to promote bacterial transmission. However, in the associated commentary, Behr et al. note that M. canettii, a relative of M. tuberculosis, produces SL-1 but is not transmitted person-to-person and that the cattle pathogen M. bovis, which emerged from M. tuberculosis, does induce coughing but does not synthesize SL-1. Future research will be needed to clarify the role of SL-1 in tuberculosis disease transmission.

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