Bitter taste receptor T2R14-Gαi coupling mediates innate immune responses to microbial quorum sensing molecules in cystic fibrosis
Nisha Singh,
Ryan H. Cunnington,
Anjali Bhagirath,
Ankita Vaishampayan,
Mohd Wasif Khan,
Tejas Gupte,
Kangmin Duan,
Abdelilah S. Gounni,
Shyamala Dakshisnamurti,
John W. Hanrahan,
Prashen Chelikani
Affiliations
Nisha Singh
Manitoba Chemosensory Biology (MCSB) research group, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Oral Biology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada
Ryan H. Cunnington
Manitoba Chemosensory Biology (MCSB) research group, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Oral Biology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada
Anjali Bhagirath
Manitoba Chemosensory Biology (MCSB) research group, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Oral Biology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada; Dalhousie University, Faculty of Dentistry, Halifax, NS, Canada
Ankita Vaishampayan
Manitoba Chemosensory Biology (MCSB) research group, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Oral Biology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada
Mohd Wasif Khan
Manitoba Chemosensory Biology (MCSB) research group, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada; Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
Tejas Gupte
Manitoba Chemosensory Biology (MCSB) research group, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Oral Biology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada
Kangmin Duan
Manitoba Chemosensory Biology (MCSB) research group, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Oral Biology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada
Abdelilah S. Gounni
Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada; Department of Immunology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
Shyamala Dakshisnamurti
Manitoba Chemosensory Biology (MCSB) research group, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada; Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
John W. Hanrahan
Department of Physiology, McGill University, Montréal, QC, Canada
Prashen Chelikani
Manitoba Chemosensory Biology (MCSB) research group, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Oral Biology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada; Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Corresponding author
Summary: Cystic fibrosis (CF) is an autosomal recessive disease characterized by microbial infection and progressive decline in lung function, leading to significant morbidity and mortality. The bitter taste receptor T2R14 is a chemosensory receptor that is significantly expressed in airways. Using a combination of cell-based assays and T2R14 knockdown in bronchial epithelial cells from CF and non-CF individuals, we observed that T2R14 plays a crucial role in the detection of bacterial and fungal signals and enhances host innate immune responses. Expression of Gαi protein is enhanced in CF bronchial epithelial cells and T2R14-Gαi specific signaling leads to increased calcium mobilization. Knockdown of T2R14 leads to reduced innate immune activation by bacterial strains deficient in quorum sensing. The results demonstrate that T2R14 helps protect against microbial infection and thus may play an important role in the innate immune defense of the CF airway epithelium.
