Helminth induced monocytosis conveys protection from respiratory
syncytial virus infection in mice.
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