Phipps S, Lam CE, Mahalingam S, Newhouse M, Ramirez R, Rosenberg HF, Foster PS, Matthaei KI
Eosinophils contribute to innate anti-viral immunity and promote clearance of respiratory syncytial virus. [JOURNAL ARTICLE]
Blood 2007 May 10.
Eosinophils are recruited to the lungs in response to respiratory syncytial virus (RSV) infection, however their role in promoting anti-viral host defence remains unclear. Here we demonstrate that eosinophils express TLRs that recognise viral nucleic acids, are activated and degranulate after ssRNA stimulation of the TLR-7-MyD88 pathway, and provide host defence 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.
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