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Abstract
Respiratory syncytial virus (RSV) infections are extremely common in early childhood but are most severe in infants in the first few months of life. Unresponsive adaptive immunity and hyporesponsive innate immunity were previously found to be the typical responses of neonate mononuclear cells (MCs) to live RSV. Investigating the mechanism of innate immune hyporesponsiveness in neonate MCs to live RSV revealed that in contrast to the previously reported low expression of interferon (IFN)-γ, IFN-α expression in response to live RSV was significantly greater than that observed in adult MCs. Inhibition of live RSV-induced IFN-α with anti-IFN-α antibodies in neonate MCs led to significant increases in innate cytokine [IFN-γ, interleukin (IL)-12, IL-18 and tumor necrosis factor (TNF)-α] but not adaptive immune cytokine [IL-2] production. Although MCs from adults responded to live RSV with upregulation of interferon regulatory factor-1 (IRF-1) mRNA, IRF-1 mRNA in RSV-treated neonate MCs was not detectable. However, in the presence of anti-IFN-α antibodies, live RSV induced detectable IRF-1 mRNA expression in neonate MCs. These data support the possibility that the severity of early life RSV-induced illnesses may occur via a mechanism in which live RSV induces IFN-α that in turn leads to innate immune suppression in neonate MCs.
Keywords:
ABBREVIATIONS
| 2′-5′AS: | = | 2′-5′ oligoadenylate synthetase |
| Con A: | = | Concanavalin A |
| GBP-2: | = | Guanylate-binding protein-2 |
| IDO: | = | Indoleamine 2,3-dioxygenase |
| IFN: | = | Interferon |
| IL: | = | Interleukin |
| iNOS: | = | Inducible nitric oxide synthase |
| IRF-1: | = | Interferon regulatory factor-1 |
| LCMV: | = | Lymphocytic choriomeningitis virus |
| LRI: | = | Lower respiratory tract infections |
| MCs: | = | Mononuclear cells |
| MLN51: | = | Metastatic lymph node 51 |
| PFU: | = | Plaque-forming units |
| PKR: | = | dsRNA-dependent protein kinase |
| PMA: | = | Phorbol myristate acetate |
| RSV: | = | Respiratory syncytial virus |
| SEB: | = | Staphylococcus enterotoxin B |
| SNP: | = | Single nucleotide polymorphisms |
| STAT: | = | Signal transducer and activation of transcription |
| TNF: | = | Tumor necrosis factor |