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

Full 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.

Author information

Author/s: Moore, Martin L (ML); Newcomb, Dawn C (DC); Parekh, Vrajesh V (VV); Van Kaer, Luc (L); Collins, Robert D (RD); Zhou, Weisong (W); Goleniewska, Kasia (K); Chi, Michael H (MH); Mitchell, Daphne (D); Boyce, Joshua A (JA); Durbin, Joan E (JE); Sturkie, Carla (C); Peebles, R Stokes (RS);

Affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN37232, USA.

Grants: AI054660 (Agency:NIAID NIH HHS) ; AI070672 (Agency:NIAID NIH HHS) ; GM015431 (Agency:NIGMS NIH HHS) ; HL069949 (Agency:NHLBI NIH HHS) ; HL090664 (Agency:NHLBI NIH HHS) ; P01 HL036110-24 (Agency:NHLBI NIH HHS) ; P01 HL036110-240017 (Agency:NHLBI NIH HHS) ; R01 AI052353-07S2 (Agency:NIAID NIH HHS) ; T32 GM07569 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol), published in United States. (Language: eng)

Reference: 2009-Aug; vol 183 (issue 3) : pp 2016-26

Dates: Created 2009/07/21; Completed 2009/08/06; Revised 2009/11/03;

PMID: 19587017, status: MEDLINE (last retrieval date: 11/4/2009, IMS Date: )

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