Neutrophils are immuno-modulatory in rhinovirus infections

Background: Neutrophils are important in controlling bacterial infections however; their role in viral infections remains unclear. Previously, we found that neutrophils respond to viral mimetics but not replication competent rhinovirus (RV). Aim: To investigate if neutrophils are activated when exposed to with RV-infected monocytes. We hypothesised that neutrophils would become activated in the presence of another activated cell. Methods: Primary human neutrophils and monocytes were co-cultured +/-RV16 or LPS, with either direct contact or separated by transwells (n=513). RV16 or LPS stimulated monocytes were exposed to killed neutrophils, neutrophil membrane or soluble neutrophil intracellular components (n=46). IL-6 and CXCL8 mRNA and protein levels were measured by qPCR and ELISA at 24h (n=47). Results: Constitutive IL-6 and CXCL8 release and LPS and RV-induced IL-6 from monocytes was inhibited when cultured with neutrophils. Direct contact with neutrophils was required for this inhibitory effect as it did not occur with transwell separation. Killed neutrophils inhibited constitutive and RV-induced monocyte derived IL-6 and CXCL8 compared to monocytes alone. Neutrophil intracellular components inhibited monocyte derived IL-6 and CXCL8 constitutively and with stimulation compared to monocytes alone, except LPS induced CXCL8. RV induced monocyte IL-6 and CXCL8 mRNA was reduced when monocytes were cultured with neutrophil intracellular components. Conclusion: We describe a novel anti-inflammatory property of neutrophils dependent on cell contact and neutrophil mediator release which may be important in the pathogenesis of viral induced asthma exacerbations