IL-13 is sufficient for respiratory syncytial virus G glycoprotein-induced eosinophilia after respiratory syncytial virus challenge.

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.

• Authors: Teresa R Johnson, Robert A Parker, Joyce E Johnson, Barney S Graham
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 170 Issue 4 Pg. 2037-45 (Feb 15 2003) ISSN: 0022-1767 [Print] United States
• PMID: 12574374 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Viral
• Cytokines
• HN Protein
• Interleukin-13
• Receptors, Interleukin-4
• Respiratory Syncytial Virus Vaccines
• Vaccines, Inactivated
• Viral Envelope Proteins
• attachment protein G
• Formaldehyde
• Interleukin-4

Topics

• Animals
• Antibodies, Viral (metabolism)
• Antibody Specificity
• Cell Line
• Cytokines (biosynthesis)
• Formaldehyde (pharmacology)
• HN Protein (immunology)
• Humans
• Immunization
• Inflammation (immunology, virology)
• Interleukin-13 (antagonists & inhibitors, physiology)
• Interleukin-4 (antagonists & inhibitors, physiology)
• Lung (immunology, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Neutralization Tests
• Pulmonary Eosinophilia (immunology, pathology, virology)
• Receptors, Interleukin-4 (deficiency, genetics)
• Respiratory Syncytial Virus Infections (immunology, pathology, virology)
• Respiratory Syncytial Virus Vaccines (administration & dosage, immunology)
• Respiratory Syncytial Viruses (immunology)
• Th2 Cells (immunology, metabolism)
• Vaccines, Inactivated (administration & dosage, immunology)
• Vaccinia virus (immunology)
• Viral Envelope Proteins
• Viral Load