title: Inflammatory response of mast cells during influenza A virus infection is mediated by active infection and RIG-I signaling.
abstract: Influenza A virus (IAV) is a major respiratory pathogen of both humans and animals. The lung is protected from pathogens by alveolar epithelial cells, tissue-resident alveolar macrophages, dendritic cells, and mast cells. The role of alveolar epithelial cells, endothelial cells, and alveolar macrophages during IAV infection has been studied previously. In this study, we address the role of mast cells during IAV infection. Respiratory infection with A/WSN/33 causes significant disease and immunopathology in C57BL/6 mice but not in B6.Cg-Kit(W-sh) mice, which lack mast cells. During in vitro coculture, A/WSN/33 caused mast cells to release histamine, secrete cytokines and chemokines, and produce leukotrienes. Moreover, when mast cells were infected with IAV, the virus did not replicate within mast cells. Importantly, human H1N1, H3N2, and influenza B virus isolates also could activate mast cells in vitro. Mast cell production of cytokines and chemokines occurs in a RIG-I/MAVS-dependent mechanism; in contrast, histamine production occurred through a RIG-I/MAVS-independent mechanism. Our data highlight that, following IAV infection, the response of mast cells is controlled by multiple receptors. In conclusion, we identified a unique inflammatory cascade activated during IAV infection that could potentially be targeted to limit morbidity following IAV infection.
authors.affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, MT 59718, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Graham
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Hilmer
authors.forename: Julianne M
authors.initials: JM
authors.lastname: Zickovich
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Obar
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000276:immunology / Q000378:metabolism*; D006632:Histamine / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015289:Leukotrienes / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D050800:STAT6 Transcription Factor / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D015289:Leukotrienes; D008565:Membrane Proteins; D050800:STAT6 Transcription Factor; D006632:Histamine; D053487:DEAD-box RNA Helicases