Asthmatic Bronchial Smooth Muscle Increases CCL5-Dependent Monocyte Migration in Response to Rhinovirus-Infected Epithelium.

Benoit Allard,Alexis Celle,Alexis Celle,Hannah Levardon,Matthieu Thumerel,Matthieu Thumerel,Matthieu Thumerel,Elise Maurat,Patrick Berger,Patrick Berger,Patrick Berger,Hannah Levardon,Thomas Trian,Thomas Trian,Elise Maurat,Pierre Olivier Girodet,Pierre Olivier Girodet,Pierre Olivier Girodet,Pauline Esteves

doi:10.3389/fimmu.2019.02998

Abstract

Asthma exacerbations, a major concern in therapeutic strategies, are most commonly triggered by viral respiratory infections, particularly with human rhinovirus (HRV). Infection of bronchial epithelial (BE) cells by HRV triggers inflammation, notably monocyte recruitment. The increase of bronchial smooth muscle (BSM) mass in asthma, a hallmark of bronchial remodeling, is associated with the annual rate of exacerbations. The aim of the present study was to assess whether or not BSM could increase monocyte migration induced by HRV-infected BE. We used an advanced in vitro model of co-culture of human BE cells in air-liquid interface with human BSM cells from control and asthmatic patients. Inflammation triggered by HRV infection (HRV-16, MOI 0.1, 1 h) was assessed at 24 h with transcriptomic analysis and multiplex ELISA. In vitro CD14+ monocyte migration was evaluated with modified Boyden chamber. Results showed that HRV-induced monocyte migration was substantially increased in the co-culture model with asthmatic BSM, compared with control BSM. Furthermore, the well-known monocyte migration chemokine, CCL2, was not involved in this increased migration. However, we demonstrated that CCL5 was further increased in the asthmatic BSM co-culture and that anti-CCL5 blocking antibody significantly decreased monocyte migration induced by HRV-infected BE. Taken together, our findings highlight a new role of BSM cells in HRV-induced inflammation and provide new insights in mucosal immunology which may open new opportunities for prevention and/or treatment of asthma exacerbation.

Highlights

Asthma is a chronic respiratory disease characterized by chronic inflammation, bronchial hyperresponsiveness and bronchial remodeling
Anti-CCL5 neutralizing antibody did not decrease monocyte migration in human rhinovirus (HRV)-infected-bronchial epithelial (BE) co-cultured with control bronchial smooth muscle (BSM) cells (Figure 4B), whereas it abolished the increased monocyte migration in HRV-infected-BE co-cultured with asthmatic BSM cells (Figure 4C). These results showed that the BSM from asthmatic patients increased the effects of HRV infection of the BE in terms of both pro-inflammatory response and monocyte migration in a CCL5-dependent manner
We focused our attention on the effects of HRV infected-BE on monocytes migration

Summary

Introduction

Asthma is a chronic respiratory disease characterized by chronic inflammation, bronchial hyperresponsiveness and bronchial remodeling. Asthma exacerbations still represent a major concern in therapeutic strategies since they are characterized by an increase in symptoms and a decrease in lung function that is sufficient to require a change in treatment [1]. Asthmatic Airways Increase Monocyte Migration exacerbations have been often associated with viral respiratory infections, with an estimated rate of 65–85% of all viral exacerbations in children and 50% in adults being caused by human rhinovirus (HRV) [2]. HRV infection of BE triggered the release of a various range of mediators, such as antiviral interferons and pro-inflammatory cytokines [4]. HRVinfected BE produced chemokines, such as IL-25, IL-33, and thymic stromal lymphopoietin, inducing immune cell migration toward lung tissue and subsequent inflammation [5]

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