Mast cells support lung eosinophil homeostasis and the acute innate immune response to respiratory syncytial virus

Abstract

Abstract As tissue-resident immune cells, mast cells release inflammatory agents in response to local viral infections. Here, we analyze Cpa3-Cre ; Mcl-1 fl/fl mice, which lack mast cells, to study the consequences of mast cell deficiency during respiratory syncytial virus (RSV) infection. At the early stages of RSV infection, mast cell-deficient mice exhibit higher viral loads, greater weight loss and exacerbated lung tissue damage when compared to control mice. Mast cell deficiency also decreases eosinophil recruitment, while increasing the influx of inflammatory monocytes and the levels of CXCL10, CCL4, and TNF in lung tissue. Reconstitution of bone-marrow–derived mast cells into mast cell-deficient mice restores eosinophil responses and protection from RSV infection, as well as repletes lung eosinophil numbers and GM-CSF levels in non-RSV conditions. Our data thus demonstrate that mast cells support an effective antiviral response and lung protection early in RSV infection and also help maintain lung eosinophil homeostasis, thereby placing them as important regulators of antiviral defense.