Respiratory syncytial virus synergizes with Th2 cytokines to induce optimal levels of TARC/CCL17.
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.
Monick
Martha M
MM
Department of Internal Medicine, University of Iowa Carver College of Medicine and Veterans Administration Medical Center, Iowa City, IA 52242, USA. martha-monick@uiowa.edu
Powers
Linda S
LS
Hassan
Ihab
I
Groskreutz
Dayna
D
Yarovinsky
Timur O
TO
Barrett
Christopher W
CW
Castilow
Elaine M
EM
Tifrea
Delia
D
Varga
Steven M
SM
Hunninghake
Gary W
GW
D000818:Animals; D045744:Cell Line, Tumor; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007156:Immunologic Memory; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018121:Receptors, Cytokine / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism* / Q000821:virology
C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D019742:Chemokines, CC; C104577:IP10-Mig receptor; D018121:Receptors, Cytokine