Unaltered influenza disease outcomes in swine prophylactically treated with α-galactosylceramide. (January 2021)

• Record Type: Journal Article
• Authors: Gu, Weihong; Madrid, Darling Melany D.; Yang, Guan; Artiaga, Bianca L.; Loeb, Julia C.; Castleman, William L.; Richt, Jürgen A.; Lednicky, John A.; Driver, John P.
• Is Part Of: Developmental and comparative immunology. Volume 114(2021)
• Publication Date: 2021-01
• Subjects: Pigs -- Influenza -- Prophylactic -- Invariant natural killer T cells -- α-Galactosylceramide; IAV Influenza A virus -- iNKT cell invariant natural killer T cell -- α-GalCer α-galactosylceramide -- TCR T cell receptor -- MDSC myeloid-derived suppressor cells -- CA04 A/California/04/2009 -- HAI hemagglutination inhibition assay -- i.v intravenous -- i.m intramuscular -- i.n intranasal -- MDCK Madin Darby Canine Kidney -- PB peripheral blood -- BALF bronchoalveolar lavage fluid -- NALT nasal associated lymphoid tissue -- TBLN tracheobronchial lymph nodes; Immunology -- Periodicals; Developmental immunology -- Periodicals; 616.079
• DOI: 10.1016/j.dci.2020.103843
• Languages: English
• ISSNs: 0145-305X

Abstract

Abstract: Influenza A viruses (IAV) are a major cause of respiratory diseases in pigs. Invariant natural killer T (iNKT) cells are an innate-like T cell subset that contribute significantly to IAV resistance in mice. In the current work, we explored whether expanding and activating iNKT cells with the iNKT cell superagonist α-galactosylceramide (α-GalCer) would change the course of an IAV infection in pigs. In one study, α-GalCer was administered to pigs intramuscularly (i.m.) 9 days before infection, which systemically expanded iNKT cells. In another study, α-GalCer was administered intranasally (i.n.) 2 days before virus infection to activate mucosal iNKT cells. Despite a synergistic increase in iNKT cells when α-GalCer i.m. treated pigs were infected with IAV, neither approach reduced disease signs, lung pathology, or virus replication. Our results indicate that prophylactic use of iNKT cell agonists to prevent IAV infection is ineffective in pigs. This is significant because this type of approach has been considered for humans whose iNKT cell levels and IAV infections are more similar to those of pigs than mice. Highlights: Pigs express iNKT cells which mouse models show can inhibit influenza infections. INKT cell levels increased in pigs treated with the NKT-ligand α-galactosylceramide. INKT cell concentrations further increased after influenza infection. Pre-expanding iNKT cells did not limit lung pathology or virus replication in pigs.