IL-13 is sufficient for respiratory syncytial virus G glycoprotein-induced eosinophilia after respiratory syncytial virus challenge.
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.
Johnson
Teresa R
TR
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive MSC 3017, Building 40, Bethesda, MD 20892, USA.
Parker
Robert A
RA
Johnson
Joyce E
JE
Graham
Barney S
BS
D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D000918:Antibody Specificity; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005557:Formaldehyde / Q000494:pharmacology; D015707:HN Protein / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007249:Inflammation / Q000276:immunology / Q000821:virology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009500:Neutralization Tests; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000473:pathology / Q000821:virology; D019948:Receptors, Interleukin-4 / Q000172:deficiency / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D014759:Viral Envelope Proteins; D019562:Viral Load
D000914:Antibodies, Viral; D016207:Cytokines; D015707:HN Protein; D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated; D014759:Viral Envelope Proteins; C116204:attachment protein G; D005557:Formaldehyde; D015847:Interleukin-4