Using a self-resolving influenza infection model we show that hyaluronan persists due to HA-synthase 2 activity in non-immune cells, that macrophages are trapped within this matrix, that HA is significantly modified by addition of HCs from IαI and that the system can be reversed, leading to improved lung function, by administration of haluronidase intransally. Here, HAS2 is linked to influenza.