Bitter Taste Receptor T2R14 Modulates Gram-Positive Bacterial Internalization and Survival in Gingival Epithelial Cells

International Journal of Molecular Sciences

Rajinder P. Bhullar¹  Anjali Yadav Bhagirath¹  Nisha Singh¹  Prashen Chelikani¹  Kangmin Duan¹  Manoj Reddy Medapati¹  Robert J. Schroth¹ 

[1] Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Rady Faculty of Health Sciences, Dr. Gerald Niznick College of Dentistry, University of Manitoba, 780 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada;

关键词: gingival epithelial cell;    G-protein-coupled receptor (GPCR);    Gram-positive bacteria;    host-microbe interaction;    innate immunity;    internalization;   

DOI  :  10.3390/ijms22189920

来源: DOAJ

【 摘 要 】

Bitter-taste receptors (T2Rs) have emerged as key players in host–pathogen interactions and important modulators of oral innate immunity. Previously, we reported that T2R14 is expressed in gingival epithelial cells (GECs) and interacts with competence stimulating peptides (CSPs) secreted by the cariogenic Streptococcus mutans. The underlying mechanisms of the innate immune responses and physiological effects of T2R14 on Gram-positive bacteria are not well characterized. In this study, we examined the role of T2R14 in internalization and growth inhibitory effects on Gram-positive bacteria, namely Staphylococcus aureus and S. mutans. We utilized CRISPR-Cas9 T2R14 knockdown (KD) GECs as the study model to address these key physiological mechanisms. Our data reveal that the internalization of S. aureus is significantly decreased, while the internalization of S. mutans remains unaffected upon knockdown of T2R14 in GECs. Surprisingly, GECs primed with S. mutans CSP-1 resulted in an inhibition of growth for S. aureus, but not for S. mutans. The GECs infected with S. aureus induced T2R14-dependent human β-defensin-2 (hBD-2) secretion; however, S. mutans–infected GECs did not induce hBD-2 secretion, but induced T2R14 dependent IL-8 secretion. Interestingly, our results show that T2R14 KD affects the cytoskeletal reorganization in GECs, thereby inhibiting S. aureus internalization. Our study highlights the distinct mechanisms and a direct role of T2R14 in influencing physiological responses to Gram-positive bacteria in the oral cavity.

【 授权许可】

Unknown