Chemokine-receptor upregulation and disease severity in respiratory syncytial virus infection

Clin Immunol. 2008 Jul;128(1):85-93. doi: 10.1016/j.clim.2008.03.460. Epub 2008 Apr 25.

Abstract

Respiratory Syncytial Virus (RSV) infection is an important cause of severe infant bronchiolitis, partly due to lower airway inflammation orchestrated by virus-induced chemokine secretion. Chemokine receptors may therefore be therapeutic targets. We investigated RSV-induced chemokine receptor (CCR) 1, 2 and 5 surface expressions in a cellular model and in infants. RSV infection increased human monocytic CCR1, 2 and 5 expression, as assessed by FACS, via replication-dependent mechanisms. CCR1 and CCR5 levels peaked at 36 h and CCR2 levels at 48 h. Monocytes from infants with RSV-bronchiolitis significantly increased CCR1 expression after ex vivo RSV infection compared to controls. Expression of CCR5 also increased, and correlated with CCR1 expression (r=0.78, p<0.0001). CCR1 upregulation correlated with disease severity markers. Monocyte CCR1 receptors were functionally active as stimulation resulted in calcium influx. CCR1/5 blocking strategies may be useful in decreasing cellular inflammation in RSV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Female
  • Flow Cytometry
  • Humans
  • Infant
  • Male
  • Monocytes / metabolism*
  • Receptors, CCR1 / biosynthesis*
  • Receptors, CCR2 / biosynthesis*
  • Receptors, CCR5 / biosynthesis*
  • Respiratory Syncytial Virus Infections / metabolism*
  • Respiratory Syncytial Virus Infections / physiopathology*
  • Up-Regulation

Substances

  • CCR1 protein, human
  • CCR2 protein, human
  • Receptors, CCR1
  • Receptors, CCR2
  • Receptors, CCR5