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* Department of Medicine,
Department of Microbiology and Immunology, and
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232;
Department of Medicine and
¶ Department of Pediatrics, Harvard Medical School, Boston. MA 02115;
|| Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston, MA 02115;
# Children’s Research Institute, Children’s Hospital, Columbus, OH 43205;
** Department of Pediatrics, Division of Pediatric Pathology, College of Medicine and Public Health, Ohio State University, Columbus, OH 43210;
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322
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+Fc
RI+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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants HL069949, AI054660, HL090664, AI070672, GM015431, and T32 GM07569, The American Academy of Allergy, Asthma, and Immunology Education and Research Trust Award, and The Thrasher Research Foundation New Researcher Award.
2 Current address: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA.
3 Address correspondence and reprint requests to Dr. R. Stokes Peebles, Jr., Department of Medicine, T-1218 MCN, Vanderbilt University Medical Center, Nashville, TN 37232-2650. E-mail address: stokes.peebles{at}vanderbilt.edu
4 Abbreviations used in this paper: RSV, respiratory syncytial virus; i.n., intranasal(ly); 
-GalCer, -galactosylceramide; p.i., post-infection; BMMC, bone marrow-derived mast cell; DC. dendritic cell.
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