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Glucagon-like peptide-1 receptor signaling attenuates RSV-induced type 2 responses and immunopathology
Monday, March 6, 2017: 2:15 PM
Rooms B308-B309 (Georgia World Congress Center, Building B)
Stokes Peebles, MD FAAAAI, , , , , ,
Rationale: Glucagon-like peptide-1 receptor (GLP-1R) agonists are a well-accepted and safe treatment for Type II diabetes. Although GLP-1R agonists mainly act to potentiate insulin and suppress glucagon secretion, recent evidence suggests that GLP-1R signaling also has anti-inflammatory effects through unclear mechanisms. Severe RSV-associated illness is in part caused by IL-13 production, which mediates the mucus production that directly contributes to airway obstruction and respiratory failure. We hypothesize that GLP-1R signaling inhibits IL-13-mediated immunopathology of RSV 12/12-6, a strain of RSV that was isolated from a hospitalized infant with severe lower respiratory tract infection and bronchiolitis.

Methods: Balb/c WT mice were infected with RSV 12/12-6. GLP-1R agonist or vehicle was administered subcutaneously twice daily beginning 2 days prior to infection. Mice were euthanized and BALs and lungs were collected for cell differentials, histopathology, AHR, ELISA, flow cytometry, or qPCR.

Results: GLP-1R agonist treatment decreased airway inflammation, airway reactivity, and airway mucus production in RSV 12/12-6-infected mice. GLP-1R agonist treatment decreased total lung IL-13 levels, with concurrent decreases in lung IL-13-producing group 2 innate lymphoid cell (ILC2), CD4+ Th2 cell, and basophil numbers. The GLP-1R agonist prevented airway inflammation, and did not impact viral load, anti-viral interferon and antibody production during secondary RSV infection. Relative to the respective mock-infected groups, RSV-infected GLP-1R agonist treated mice did not have increased weight loss compared to vehicle treated mice.

Conclusions: These data suggest that GLP-1R signaling protects against type 2-mediated immunopathology during RSV infection.