Differential MAPK and cytokine responses to human rhinovirus by human macrophages is a function of receptor‐mediated signal transduction

Abstract

In both children and adults, asthma exacerbations are caused primarily by viral respiratory infections, with human rhinovirus (HRV) being the most common infectious agent detected. Major and minor group rhinoviruses enter cells by binding to the cell surface molecules ICAM‐1 and LDL‐R respectively that are present on both macrophages and epithelial cells. Although epithelial cells are the site of productive HRV infection, previous studies have implicated macrophages in establishing the cytokine dysregulation relevant to asthma exacerbations in response to rhinovirus challenge. Even though major and minor group rhinoviruses are nearly genetically identical, differences in cytokine release and MAPK activation were observed indicating a differential virus response. Major and minor group HRV elicited differential production of the asthma relevant cytokines CCL20, MCP‐1 and IL‐10. Furthermore, differential activation of the MAPKs p38, JNK and ERK5 was observed between the major and minor group HRV treatments. This is the first report of genetically similar viruses with different receptors eliciting dissimilar cytokine release and MAPK activation from macrophages suggesting that receptor dependence plays a role in establishing the inflammatory microenvironment initiated in the human airway upon exposure to rhinovirus. This work was supported by the McNair program, NIH R15 AI065505‐01A1 and NSF 0521112.