NK cell deficiency predisposes to viral-induced Th2-type allergic inflammation via epithelial-derived IL-25.
Severe respiratory syncytial virus (RSV) infection has long been associated with an increased risk for the development of childhood asthma and exacerbations of this disorder. Despite much research into the induction of Th2 responses by allergens and helminths, the factors associated with viral infection that predispose to Th2-regulated asthma remain unknown. Recently, clinical studies have shown reduced numbers of NK cells in infants suffering from a severe RSV infection. Here we demonstrate that NK cell deficiency during primary RSV infection of BALB/c mice results in the suppression of IFN-γ production and the development of an RSV-specific Th2 response and subsequent allergic lung disease. The outgrowth of the Th2 responses was dependent on airway epithelial cell-derived IL-25, which induced the upregulation of the notch ligand Jagged1 on dendritic cells. This study identifies a novel pathway underlying viral-driven Th2 responses that may have functional relevance to viral-associated asthma.
Kaiko
Gerard E
GE
Centre for Asthma and Respiratory Diseases, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, Australia.
Phipps
Simon
S
Angkasekwinai
Pornpimon
P
Dong
Chen
C
Foster
Paul S
PS
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018893:Bronchoalveolar Lavage; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000821:virology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000821:virology; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D000072100:Jagged-1 Protein; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C442281:Mydgf protein, mouse; D000072099:Serrate-Jagged Proteins