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

iScience (Dec 2024)

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

Journal volume & issue: Vol. 27, no. 12
p. 111286

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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