Human upper airway epithelium produces nitric oxide in response to Staphylococcus epidermidis.

BACKGROUND: Nitric oxide (NO) is produced by sinonasal epithelial cells as part of the innate immune response against bacteria. We previously described bitter-taste-receptor-dependent and -independent NO responses to product(s) secreted by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. We hypothesized that sinonasal epithelium would be able to detect the gram-positive, coagulase-negative bacteria Staphylococcus epidermidis and mount a similar NO response.
METHODS: Sinonasal air-liquid interface cultures were treated with conditioned medium (CM) from lab strains and clinical isolates of coagulase-negative staphylococci and S aureus. NO production was quantified by fluorescence imaging. Bitter taste receptor signaling inhibitors were utilized to characterize the pathway responsible for NO production in response to S epidermidis CM.
RESULTS: S epidermidis CM contains a low-molecular-weight, heat, and protease-stabile product that induces an NO synthase (NOS)-mediated NO production that is less robust than the response triggered by S aureus CM. The S epidermidis CM-stimulated NO response is not inhibited by antagonists of phospholipase C isoform β-2 nor the transient receptor potential melastatin isoform 5 ion channel, both critical to bitter taste signaling.
CONCLUSION: This study identifies an NO-mediated innate defense response in sinonasal epithelium elicited by S epidermidis product(s). The active bacterial product is likely a small, nonpeptide molecule that stimulates a pathway independent of bitter taste receptors. Although the NO response to S epidermidis is less vigorous compared with S aureus, the product(s) share similar characteristics. Together, the responses to staphylococci species may help explain the pathophysiology of upper respiratory infections.