MIP-3alpha/CCL20 expression is highly induced in respiratory epithelium and in human subjects infected with rhinoviruses

Abstract

Rationale Macrophage Inflammatory Protein-3alpha (MIP-3a) is a chemokine that binds specifically to CCR6 on naïve dendritic cells and memory lymphocytes, and has been shown to increase in animal models of allergic and virus-induced pulmonary inflammation. It is our hypothesis that viral respiratory infections in humans will also cause an increase in MIP-3a. Methods To evaluate this possibility, the effects of RV1A infection on respiratory epithelial cell mRNA expression were analyzed using Affymetrix Human Focus GeneChips. In addition, nasal lavage samples obtained from subjects inoculated with RV16 were analyzed for MIP-3a by ELISA. Results The GeneChip analysis demonstrated that RV1A infection induced MIP-3a mRNA expression in bronchial epithelial cells starting at 4 hours and peaking (14-fold induction) at 16 hours. In the nasal samples from virus-infected subjects, baseline levels of MIP-3a protein were low (median 23 pg/ml), but significantly increased during the acute RV16 cold (p=0.019). On day 4 of infection, a 30-fold increase in MIP-3a (median 690 pg/mL) was seen compared to baseline ( p<0.05). Conclusions Rhinovirus infection in humans is a potent inducer of MIP-3a in vitro and in vivo. Known effects of MIP-3a on dendritic cells suggest that it could be an important contributor to the early antiviral and/or pro-inflammatory immune responses. Additional studies are needed to explore a potential link to the generation of respiratory symptoms and airway dysfunction during RV infections.