Respiratory syncytial virus infection influences tight junction integrity

Jeannette I Kast, Amanda J McFarlane, Anna Głobińska, Milena Sokolowska, Paulina Wawrzyniak, Marek Sanak, Jürgen Schwarze, Cezmi A Akdis, Kerstin Wanke

Research output: Contribution to journalArticlepeer-review

Abstract

Background Respiratory syncytial virus (RSV) is an important risk factor of asthma development and is responsible for severe respiratory tract infections. However, the influence of RSV infection on barrier function of bronchial epithelial cells in vitro and in vivo is still unclear. Objective The aim of this study was to analyze the role of RSV in tight junction (TJ) regulation and to compare epithelial integrity between asthmatic and healthy individuals upon RSV infection. Methods Healthy and asthmatic human bronchial epithelial cells (HBECs) were differentiated at air-liquid interface (ALI) and infected with RSV and UV-irradiated RSV. TJ expression and their integrity were analysed by qPCR, transepithelial resistance (TER) and paracellular flux. To determine the effect in vivo, Balb/c mice were intranasally infected with RSV or UV-irradiated RSV A2. Bronchoalveolar lavage and TJ integrity were analysed on days 1, 2, 4 and 6 post infection by qPCR, bioplex and confocal microscopy. Results RSV increased barrier integrity in ALI cultures of HBEC from healthy subjects, but no effect was found in HBECs from asthmatics. This was not associated with an increase in TJ mRNA expression. In vivo, RSV induced lung inflammation in mice and downregulated claudin-1 and occludin mRNA expression in the whole lungs. Surprisingly, RSV infection was not observed in bronchial epithelial cells, but was found in the lung parenchyma. Decreased expression of occludin upon RSV infection was visible in mouse bronchial epithelial cells in confocal microscopy. However, there was no regulation of claudin-1 and claudin-7 at protein level. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalClinical & Experimental Immunology
Early online date30 Aug 2017
DOIs
Publication statusE-pub ahead of print - 30 Aug 2017

Keywords

  • Journal Article

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