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

Moore ML, Newcomb DC, Parekh VV, Van Kaer L, Collins RD, Zhou W, Goleniewska K, Chi MH, Mitchell D, Boyce JA, Durbin JE, Sturkie C, Peebles RS
J Immunol. 2009 183 (3): 2016-26

PMID: 19587017 · PMCID: PMC3755459 · DOI:10.4049/jimmunol.0803167

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.

MeSH Terms (11)

Animals Basophils Flow Cytometry Gene Expression Regulation Immunophenotyping Interleukin-4 Lung Mice Mice, Inbred BALB C Respiratory Syncytial Virus Infections STAT1 Transcription Factor

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