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Innate Immun. 2014 Aug;20(6):606-17. doi: 10.1177/1753425913503386. Epub 2013 Sep 17.

Mouse nasal epithelial innate immune responses to Pseudomonas aeruginosa quorum-sensing molecules require taste signaling components.

Author information

1
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA.
2
Monell Chemical Senses Center and Philadelphia VA Medical Center Surgical Services, Philadelphia, PA, USA.
3
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA Surgical Services, Philadelphia Veterans Administration Medical Center, Philadelphia, PA, USA noam.cohen@uphs.upenn.edu.

Abstract

We previously observed that the human bitter taste receptor T2R38 is an important component of upper respiratory innate defense because it detects acyl homoserine lactone (AHL) quorum-sensing molecules secreted by Gram-negative bacteria. T2R38 activation in human sinonasal epithelial cells stimulates calcium and NO signals that increase mucociliary clearance, the major physical respiratory defense against inhaled pathogens. While mice do not have a clear T2R38 ortholog, they do have bitter taste receptors capable of responding to T2R38 agonists, suggesting that T2R-mediated innate immune mechanisms may be conserved in mice. We examined whether AHLs activate calcium and NO signaling in mouse nasal epithelial cells, and utilized pharmacology, as well as cells from knockout mice lacking important components of canonical taste signal transduction pathways, to determine if AHL-stimulated responses require taste signaling molecules. We found that AHLs stimulate calcium-dependent NO production that increases mucociliary clearance and thus likely serves an innate immune role against Gram-negative bacteria. These responses require PLCβ2 and TRPM5 taste signaling components, but not α-gustducin. These data suggest the mouse may be a useful model for further studies of T2R-mediated innate immunity.

KEYWORDS:

Acyl-homoserine lactone; T2R bitter taste receptor; chronic rhinosinusitis; innate immunity; mucociliary clearance; nitric oxide

PMID:
24045336
PMCID:
PMC4811369
DOI:
10.1177/1753425913503386
[Indexed for MEDLINE]
Free PMC Article

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