Respiratory syncytial virus synergizes with Th2 cytokines to induce optimal levels of TARC/CCL17

J Immunol. 2007 Aug 1;179(3):1648-58. doi: 10.4049/jimmunol.179.3.1648.

Abstract

Respiratory syncytial virus (RSV) is a ubiquitous virus that preferentially infects airway epithelial cells, causing asthma exacerbations and severe disease in immunocompromised hosts. Acute RSV infection induces inflammation in the lung. Thymus- and activation-regulated chemokine (TARC) recruits Th2 cells to sites of inflammation. We found that acute RSV infection of BALB/c mice increased TARC production in the lung. Immunization of BALB/c mice with individual RSV proteins can lead to the development of Th1- or Th2-biased T cell responses in the lung after RSV infection. We primed animals with a recombinant vaccinia virus expressing either the RSV fusion (F) protein or the RSV attachment (G) protein, inducing Th1- and Th2-biased pulmonary memory T cell responses, respectively. After RSV infection, TARC production significantly increased in the vaccinia virus G-primed animals only. These data suggest a positive feedback loop for TARC production between RSV infection and Th2 cytokines. RSV-infected lung epithelial cells cultured with IL-4 or IL-13 demonstrated a marked increase in the production of TARC. The synergistic effect of RSV and IL-4/IL-13 on TARC production reflected differential induction of NF kappa B and STAT6 by the two stimuli (both are in the TARC promoter). These findings demonstrate that RSV induces a chemokine TARC that has the potential to recruit Th2 cells to the lung.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chemokine CCL17
  • Chemokines, CC / biosynthesis*
  • Chemokines, CC / metabolism
  • Chemokines, CC / physiology
  • Chemotaxis, Leukocyte / immunology
  • Disease Models, Animal
  • Humans
  • Immunologic Memory
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Cytokine / biosynthesis
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / metabolism
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Viruses / immunology*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / virology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism*
  • Th2 Cells / virology

Substances

  • Ccl17 protein, mouse
  • Chemokine CCL17
  • Chemokines, CC
  • IP10-Mig receptor
  • Receptors, Cytokine