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IL-13 Is Required for Eosinophil Entry into the Lung during Respiratory Syncytial Virus Vaccine-Enhanced Disease¹

Elaine M. Castilow^*, David K. Meyerholz and Steven M. Varga^2,*,

^* Interdisciplinary Graduate Program in Immunology, Department of Pathology, and Department of Microbiology, University of Iowa, Iowa City, IA 52242

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in children. Children previously vaccinated with a formalin-inactivated RSV vaccine experienced enhanced morbidity and mortality upon natural RSV infection. Histological analysis revealed the presence of eosinophils in the pulmonary infiltrate of the vaccinated children. Eosinophils are characteristic of Th2 responses, and Th2 cells are known to be necessary to induce pulmonary eosinophilia in RSV-infected BALB/c mice previously immunized with a recombinant vaccinia virus (vv) expressing the RSV G protein (vvG). Using IL-13-deficient mice, we find that IL-13 is necessary for eosinophils to reach the lung parenchyma and airways of vvG-immunized mice undergoing RSV challenge infection. IL-13 acts specifically on eosinophils as the magnitude of pulmonary inflammation, RSV G protein-specific CD4 T cell responses, and virus clearance were not altered in IL-13-deficient mice. After RSV challenge, eosinophils were readily detectable in the blood and bone marrow of vvG-immunized IL-13-deficient mice, suggesting that IL-13 is required for eosinophils to transit from the blood into the lung. Pulmonary levels of CCL11 and CCL22 protein were significantly reduced in IL-13-deficient mice indicating that IL-13 mediates the recruitment of eosinophils into the lungs by inducing the production of chemokines important in Th2 cell and eosinophil chemotaxis.

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 funding from the American Heart Association Predoctoral Fellowship (to E.M.C.), University of Iowa Department of Pathology (to D.K.M.), and National Institutes of Health Grant AI 063520 (to S.M.V.).

² Address correspondence and reprint requests to Dr. Steven M. Varga, Department of Microbiology, University of Iowa, 51 Newton Road, Iowa City, IA 52242. E-mail address: steven-varga{at}uiowa.edu

³ Abbreviations used in this paper: RSV, respiratory syncytial virus; FI-RSV, formalin-inactivated RSV; vv, vaccinia virus; β-gal, β-galactosidase; BAL, bronchoalveolar lavage; MBP, major basic protein; N, nucleocapsid protein.