STAT1 negatively regulates lung basophil IL-4 expression induced by respiratory syncytial virus infection

IL-4 contributes to immunopathology induced in mice by primary respiratory syncytial virus (RSV) infection. However, the cellular source of IL-4 in RSV infection is unknown. We identified CD3(-)CD49b(+) cells as the predominant source of IL-4 in the lungs of RSV-infected BALB/c mice. We ruled out T cells, NK cells, NKT cells, mast cells, and eosinophils as IL-4 expressors in RSV infection by flow cytometry. Using IL4 GFP reporter mice (4get) mice, we identified the IL-4-expressing cells in RSV infection as basophils (CD3(-)CD49b(+)FcepsilonRI(+)c-kit(-)). Because STAT1(-/-) mice have an enhanced Th2-type response to RSV infection, we also sought to determine the cellular source and role of IL-4 in RSV-infected STAT1(-/-) mice. RSV infection resulted in significantly more IL-4-expressing CD3(-)CD49b(+) cells in the lungs of STAT1(-/-) mice than in BALB/c mice. CD49b(+)IL-4(+) cells sorted from the lungs of RSV-infected STAT1(-/-) mice and stained with Wright-Giemsa had basophil characteristics. As in wild-type BALB/c mice, IL-4 contributed to lung histopathology in RSV-infected STAT1(-/-) mice. Depletion of basophils in RSV-infected STAT1(-/-) mice reduced lung IL-4 expression. Thus, we show for the first time that a respiratory virus (RSV) induced basophil accumulation in vivo. Basophils were the primary source of IL-4 in the lung in RSV infection, and STAT1 was a negative regulator of virus-induced basophil IL-4 expression.