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IL-13 is required for eosinophil entry into the lung during respiratory syncytial virus vaccine-enhanced disease
Journal article   Peer reviewed

IL-13 is required for eosinophil entry into the lung during respiratory syncytial virus vaccine-enhanced disease

Elaine M Castilow, David K Meyerholz and Steven M Varga
The Journal of immunology (1950), Vol.180(4), pp.2376-2384
02/15/2008
DOI: 10.4049/jimmunol.180.4.2376
PMID: 18250447

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Abstract

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.
Interleukin-13 - physiology Respiratory Syncytial Virus Vaccines - immunology Interleukin-13 Receptor alpha1 Subunit - deficiency Pulmonary Eosinophilia - virology Respiratory Syncytial Viruses - immunology Respiratory Syncytial Virus Infections - immunology Vaccinia virus - immunology Interleukin-13 - biosynthesis Lung - virology Female Respiratory Syncytial Virus Infections - virology Pulmonary Eosinophilia - immunology Lung - pathology Eosinophils - virology Viral Envelope Proteins - administration & dosage Pulmonary Eosinophilia - pathology Mice, Knockout Interleukin-13 Receptor alpha1 Subunit - genetics Animals Respiratory Syncytial Virus Vaccines - administration & dosage Viral Envelope Proteins - immunology Mice Mice, Inbred BALB C Chemotaxis, Leukocyte - immunology Eosinophils - cytology Respiratory Syncytial Virus Infections - pathology Lung - immunology

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