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

TY - JOUR

T1 - STAT1 negatively regulates lung basophil IL-4 expression induced by respiratory syncytial virus infection

AU - Moore, Martin L.

AU - Newcomb, Dawn C.

AU - Parekh, Vrajesh V.

AU - Van Kaer, Luc

AU - Collins, Robert D.

AU - Zhou, Weisong

AU - Goleniewska, Kasia

AU - Chi, Michael H.

AU - Mitchell, Daphne

AU - Boyce, Joshua A.

AU - Durbin, Joan E.

AU - Sturkie, Carla

AU - Peebles, R. Stokes

PY - 2009/8/1

Y1 - 2009/8/1

N2 - 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+FcεRI+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.

AB - 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+FcεRI+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.

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U2 - https://doi.org/10.4049/jimmunol.0803167

DO - https://doi.org/10.4049/jimmunol.0803167

M3 - Article

C2 - 19587017

SN - 0022-1767

VL - 183

SP - 2016

EP - 2026

JO - Journal of Immunology

JF - Journal of Immunology

IS - 3

ER -