Introduction
Respiratory syncytial virus (RSV) induced viral bronchiolitis is a major cause of infant hospitalisation worldwide1. Adult infection is frequently associated with mild respiratory illness but can also cause significant morbidity and mortality in the elderly and immunocompromised individuals2,3. There is as yet no active vaccination towards or specific therapy for RSV infection although many promising candidates are currently in clinical trials. Treatment is limited to supportive measures and prophylaxis for high risk infants with the anti-RSV F-protein antibody palivizumab, a high cost option with limited effectiveness4,5.
Novel approaches to managing RSV, and greater understanding of the immune response to infection, are still required. We have previously reported that an ongoing infection with the murine enteric helminthHeligmosomoides polygyrus (H. polygyrus ) is able to improve RSV infection outcomes by suppressing the peak viral load early in infection6. This work found that the adaptive immune response to H. polygyrus infection, the type 2 immune response, characteristic of helminthic infection and typified by robust IL-33, IL-4 and IL-13 signalling7, as well as the anti-microbial peptide LL-37 are not required for the H. polygyrus induced anti-viral immunity in the lung. Rather, type I interferon (IFN-I) signalling, induction of interferon beta (IFNβ) and interferon stimulated genes (ISGs), including Rsad2 (encoding viperin) and Oas1a are central to the H. polygyrus induced protective effect against RSV infection. Many ISGs have antiviral functions and both viperin and OAS can limit RSV infection8,9. Almost all cells of the lung have the capacity to both produce one or more of the family of IFN-Is and to respond to IFN-I signalling through the dedicated receptor IFNalpha receptor (IFNAR) 10-12. This broad potential space for IFN-I signalling led us to question which cells may be contributing toH. polygyrus induced anti-viral effects. Mononuclear phagocytes, including monocytes and macrophages, are known responders to IFN-Is and have been linked to early control of RSV infection13,14. IFN-Is can regulate monocyte recruitment during inflammation, skew hematopoietic output, and through interferon regulatory factors promote differentiation to, and polarisation of, macrophages15-18. Monocytes can also be potent produces of IFN-Is, especially IFNβ, in response to stimuli including RSV19. We therefore hypothesised that lung mononuclear phagocytes following H. polygyrus infection mediate the helminth induced protective effect against RSV infection.