Respiratory Syncytial Virus Persistence in Macrophages Downregulates Intercellular Adhesion Molecule-1 Expression and Reduces Adhesion of Non-Typeable Haemophilus influenzae

Abstract

Background: Persistence of respiratory syncytial virus (RSV) has been associated with episodes of chronic obstructive pulmonary disease (COPD); furthermore, co-infection of RSV with non-typeable Haemophilus influenzae (NTHi) is increasingly recognized as a cause of exacerbations of COPD. Objective: To study whether RSV persistence in a macrophage (Mφ)-like cell line alters NTHi uptake (adhesion and ingestion). Methods: A murine Mφ-like cell line persistently infected with RSV (MφP) was used. The effects of RSV persistence on NTHi uptake by MφP and mock-infected Mφ (MφN) were determined by flow-cytometric assays with NTHi labelled with either ethidium bromide or FITC. Expression of intercellular adhesion molecule-1 (ICAM-1), a ligand for NTHi, was determined by measuring mRNA through real-time PCR and protein by Western blot assays. Results: RSV persistence reduced both the capacity of Mφ to take up bacteria and the expression of ICAM-1 mRNA and protein. Furthermore, when ICAM-1 was blocked with anti-ICAM-1 antibody, the adhesion capacity of NTHi was significantly reduced for MφN, whereas for MφP the effect was less evident, implying that ICAM-1 participates in NTHi adhesion to Mφ. Conclusion: RSV persistence in murine Mφ diminishes their capacity to adhere and ingest NTHi through downregulation of ICAM-1 expression at the transcriptional level.