Th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, ICAM-1.
Intercellular adhesion molecule (ICAM)-1 is a cell receptor important in both human rhinovirus (HRV) attachment and immune effector cell mobilization. The level of expression of ICAM-1 by epithelial cells (EC) therefore plays a crucial role in the intricate biological phenomena underlying viral binding, host infection and consequent inflammatory events. As T-helper (Th)2 lymphocytes predominate within the asthmatic airway, the influence was evaluated of Th2-associated mediators in the modulation of ICAM-1 expression on uninfected and HRV-infected EC. H292 EC were cultured in vitro, with varying concentrations of interleukin (IL)-4, IL-5, IL-10 and IL-13 for 24 h and then infected with live HRV-14. Surface ICAM-1 expression was assessed by immunocytochemistry. Infection with HRV-14 resulted in a twofold increase in ICAM-1 expression. IL-4, IL-5, IL-10 and IL-13 produced a 2.7-5.1-fold enhancement of ICAM-1 expression of uninfected cells and caused approximately a further twofold increase in infected cells over the expression induced by HRV infection itself. Interferon-gamma in combination with each Th2-associated cytokine only slightly reduced, but did not override, the Th2-induced level of ICAM-1 expression on both uninfected and virus-infected EC. These data suggest that the effects of Th2-associated cytokines on intercellular adhesion molecule-1 expression and recovery of infectious virus are dominant over the effects of the Th1-associated cytokines such as interferon-gamma. Since the airway mucosa in atopic asthma is predominantly infiltrated by Th2 lymphocytes, these results could explain both the increased susceptibility to human rhinovirus infection in asthmatic patients and the associated exacerbation of asthma symptoms.
Dept of Respiratory Medicine, North Staffordshire Hospital Trust, UK.
A
A
Bianco
S K
SK
Sethi
J T
JT
Allen
R A
RA
Knight
M A
MA
Spiteri
D002478:Cells, Cultured; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis*; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000378:metabolism*; D010850:Picornaviridae Infections / Q000276:immunology; D011336:Probability; D012229:Rhinovirus / Q000472:pathogenicity*; D018709:Statistics, Nonparametric; D013499:Surface Properties; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation
D007378:Interleukins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma