The Effect of a TLR3 Agonist on Airway Allergic Inflammation and Viral Infection in Immunoproteasome-Deficient Mice

• Published in: Viruses Vol. 16; no. 9; p. 1384
• Main Authors: Schaunaman, Niccolette, Nichols, Taylor, Cervantes, Diana, Hartsoe, Paige, Ferrington, Deborah A., Chu, Hong Wei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.08.2024; MDPI
• Subjects: Agonists; Agonists (Biochemistry); Airway management; Allergens; allergic asthma; Animals; Antiviral agents; Antiviral drugs; Asthma; Asthma - drug therapy; Asthma - immunology; Cytokines; Development and progression; Disease Models, Animal; Drug therapy; dust mites; eosinophils; Eosinophils - immunology; Gene expression; Health aspects; Hypersensitivity; Hypersensitivity - drug therapy; Hypersensitivity - immunology; immunoproteasome; Infections; Inflammation; Inflammation - immunology; Interferon; Interferon-beta - genetics; Interferon-beta - immunology; Leukocytes; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Lung - immunology; Lung - pathology; Lung - virology; Lungs; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Picornaviridae Infections - immunology; Poly I-C - pharmacology; Polyinosinic:polycytidylic acid; Proteasome Endopeptidase Complex - metabolism; Proteolysis; Pyroglyphidae - immunology; Recurrent infection; Respiratory allergy; Respiratory tract infection; Rhinovirus; Statistical analysis; Testing; TLR3; TLR3 protein; Toll-Like Receptor 3 - agonists; Toll-Like Receptor 3 - genetics; Toll-like receptors; Viral infections; Viral Load; Virus diseases; viruses; β-Interferon; United States; United States > US; allergic asthma; rhinovirus; immunoproteasome
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v16091384

Allergic asthma is characterized by increased type 2 inflammation, including eosinophils. Subjects with allergic asthma have recurrent symptoms due to their constant exposure to environmental allergens, such as house dust mite (HDM), which can be further exacerbated by respiratory infections like rhinovirus. The immunoproteasome (IP) is a proteolytic machinery that is induced by inflammatory mediators during virus infection, but the role of the IP in airway allergic inflammation during rhinovirus infection remains unknown. Wild-type (WT) and IP knockout (KO) mice were challenged with HDM. At 48 h after the last HDM challenge, mice were infected with rhinovirus 1B (RV-A1B) for 24 h. After HDM and RV-A1B treatment, IP KO (vs. WT) mice had significantly more lung eosinophils and neutrophils, as well as a significantly higher viral load, but less IFN-beta expression, compared to WT mice. A TLR3 agonist polyinosinic-polycytidylic acid (Poly I:C) treatment after RV-A1B infection in HDM-challenged IP KO mice significantly increased IFN-beta expression and reduced viral load, with a minimal effect on the number of inflammatory cells. Our data suggest that immunoproteasome is an important mechanism functioning to prevent excessive inflammation and viral infection in allergen-exposed mice, and that Poly I:C could be therapeutically effective in enhancing the antiviral response and lessening the viral burden in lungs with IP deficiency.