Abstract
Although well studied in settings of helminth infection and allergen sensitization, the combined contributions of IL-4 and IL-13 and their signaling pathways in models of viral pathogenesis have not been reported. Using a murine model of respiratory syncytial virus (RSV) infection, we evaluated the contribution of IL-13, alone and in conjunction with IL-4, during immunization with recombinant vaccinia virus expressing RSV G glycoprotein (vvGs) or with formalin-inactivated RSV (FI-RSV). We showed that both IL-4 and IL-13 activity must be inhibited to modulate G-specific responses resulting in severe RSV-induced disease. Inhibition of IL-4 or IL-13 activity alone had minimal impact on disease in vvGs-immunized mice. However, treatment of IL-4-deficient mice with IL-13Ra during vvGs immunization reduced IL-5, IL-13, and eotaxin production and pulmonary eosinophilia after RSV challenge. In contrast, FI-RSV-induced immune responses were diminished when either IL-4 or IL-13 activity was blocked. After RSV challenge, these type 2 T cell responses were also diminished in vvGs-primed IL-4Ralpha-deficient mice. Our data suggest that secreted vvGs uses mechanisms requiring signaling through the IL-4Ralpha-chain by either IL-4 or IL-13 for induction of eosinophilia and is the first description of the relative contributions of IL-4, IL-13, and their receptors in viral pathogenesis.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Viral / metabolism
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Antibody Specificity
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Cell Line
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Cytokines / biosynthesis
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Formaldehyde / pharmacology
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HN Protein / immunology*
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Humans
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Immunization
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Inflammation / immunology
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Inflammation / virology
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Interleukin-13 / antagonists & inhibitors
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Interleukin-13 / physiology*
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Interleukin-4 / antagonists & inhibitors
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Interleukin-4 / physiology
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Lung / immunology
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Lung / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Neutralization Tests
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Pulmonary Eosinophilia / immunology*
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Pulmonary Eosinophilia / pathology
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Pulmonary Eosinophilia / virology
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Receptors, Interleukin-4 / deficiency
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Receptors, Interleukin-4 / genetics
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Respiratory Syncytial Virus Infections / immunology*
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Respiratory Syncytial Virus Infections / pathology
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Respiratory Syncytial Virus Infections / virology
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Respiratory Syncytial Virus Vaccines / administration & dosage
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Respiratory Syncytial Virus Vaccines / immunology
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Respiratory Syncytial Viruses / immunology*
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Vaccines, Inactivated / administration & dosage
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Vaccines, Inactivated / immunology
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Vaccinia virus / immunology
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Viral Envelope Proteins
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Viral Load
Substances
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Antibodies, Viral
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Cytokines
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HN Protein
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Interleukin-13
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Receptors, Interleukin-4
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Respiratory Syncytial Virus Vaccines
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Vaccines, Inactivated
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Viral Envelope Proteins
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attachment protein G
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Formaldehyde
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Interleukin-4