title: STAT1 negatively regulates lung basophil IL-4 expression induced by respiratory syncytial virus infection.
abstract: 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.
authors: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN37232, USA.
authors: Martin L
authors: ML
authors: Moore
authors: Dawn C
authors: DC
authors: Newcomb
authors: Vrajesh V
authors: VV
authors: Parekh
authors: Luc
authors: L
authors: Van Kaer
authors: Robert D
authors: RD
authors: Collins
authors: Weisong
authors: W
authors: Zhou
authors: Kasia
authors: K
authors: Goleniewska
authors: Michael H
authors: MH
authors: Chi
authors: Daphne
authors: D
authors: Mitchell
authors: Joshua A
authors: JA
authors: Boyce
authors: Joan E
authors: JE
authors: Durbin
authors: Carla
authors: C
authors: Sturkie
authors: R Stokes
authors: RS
authors: Peebles
mesh_terms: D000818:Animals; D001491:Basophils / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000235:genetics*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000502:physiology*
chemical_list: D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015847:Interleukin-4