Abstract:
Background Respiratory syncytial virus (RSV) infection in
infants is a major cause of viral bronchiolitis and hospitalisation. We
have previously shown in a murine model that ongoing infection with the
gut helminth Heligmosomoides polygyrus (H. polygyrus )
protects against RSV infection through type I interferon (IFN-I)
dependent reduction of viral load. Yet, the cellular basis for this
protection has remained elusive. Given that recruitment of mononuclear
phagocytes to the lung is critical for early RSV infection control, we
assessed their role in this coinfection model.
Methods Mice were infected by oral gavage with H.
polygyrus . Myeloid immune cell populations were assessed by flow
cytometry in lung, blood and bone marrow throughout infection and after
secondary infection with RSV. Monocyte numbers were depleted by
anti-CCR2 antibody or increased by intravenous transfer of enriched
monocytes.
Results H. polygyrus infection induces bone marrow
monopoiesis, increasing circulatory monocytes and lung mononuclear
phagocytes in a IFN-I signalling dependent manner. This expansion causes
enhanced lung mononuclear phagocyte counts early in RSV infection that
may contribute to the reduction of RSV load. Depletion or
supplementation of circulatory monocytes prior to RSV infection confirms
that these are both necessary and sufficient for helminth induced
antiviral protection.
Conclusions H. polygyrus infection induces systemic
monocytosis contributing to elevated mononuclear phagocyte numbers in
the lung. These cells are central to an anti-viral effect that reduces
the peak viral load in RSV infection. Treatments to promote or modulate
these cells may provide novel paths to control RSV infection in high
risk individuals.