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.