title: Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus.
abstract: Eosinophils are recruited to the lungs in response to respiratory syncytial virus (RSV) infection; however, their role in promoting antiviral host defense remains unclear. Here, we demonstrate that eosinophils express TLRs that recognize viral nucleic acids, are activated and degranulate after single-stranded RNA (ssRNA) stimulation of the TLR-7-MyD88 pathway, and provide host defense against RSV that is MyD88 dependent. In contrast to wild-type mice, virus clearance from lung tissue was more rapid in hypereosinophilic (interleukin-5 transgenic) mice. Transfer of wild-type but not MyD88-deficient eosinophils to the lungs of RSV-infected wild-type mice accelerated virus clearance and inhibited the development of airways hyperreactivity. Similar responses were observed when infected recipient mice were MyD88 deficient. Eosinophils isolated from infected hypereosinophilic MyD88-sufficient but not MyD88-deficient mice expressed greater amounts of IFN regulatory factor (IRF)-7 and eosinophil-associated ribonucleases EAR-1 and EAR-2. Hypereosinophilia in the airways of infected mice also correlated with increased expression of IRF-7, IFN-beta, and NOS-2, and inhibition of NO production with the NOS-2 inhibitor L-NMA partially reversed the accelerated virus clearance promoted by eosinophils. Collectively, our results demonstrate that eosinophils can protect against RSV in vivo, as they promote virus clearance and may thus limit virus-induced lung dysfunction.
authors.affiliation: Centre for Asthma and Respiratory Diseases (CARD), School of Biomedical Sciences, University of Newcastle, Newcastle, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Phipps
authors.forename: Chuan En
authors.initials: CE
authors.lastname: Lam
authors.forename: Suresh
authors.initials: S
authors.lastname: Mahalingam
authors.forename: Matthew
authors.initials: M
authors.lastname: Newhouse
authors.forename: Ruben
authors.initials: R
authors.lastname: Ramirez
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
authors.forename: Paul S
authors.initials: PS
authors.lastname: Foster
authors.forename: Klaus I
authors.initials: KI
authors.lastname: Matthaei
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047208:Eosinophil-Derived Neurotoxin / Q000096:biosynthesis / Q000276:immunology; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D007113:Immunity, Innate; D050839:Interferon Regulatory Factor-7 / Q000096:biosynthesis / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D050839:Interferon Regulatory Factor-7; D015848:Interleukin-5; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012367:RNA, Viral; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D009569:Nitric Oxide; D016899:Interferon-beta; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C479821:Ear2 protein, mouse; D047208:Eosinophil-Derived Neurotoxin