Abstract
Rhinovirus infection is associated with the majority of asthma exacerbations. The role of fractalkine in anti-viral (type 1) and pathogenic (type 2) responses to rhinovirus infection in allergic asthma is unknown. To determine whether (1) fractalkine is produced in airway cells and in peripheral blood leucocytes, (2) rhinovirus infection increases production of fractalkine and (3) levels of fractalkine differ in asthmatic compared to non-asthmatic subjects. Fractalkine protein and mRNA levels were measured in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from non-asthmatic controls (n = 15) and mild allergic asthmatic (n = 15) subjects. Protein levels of fractalkine were also measured in macrophages polarised ex vivo to give M1 (type 1) and M2 (type 2) macrophages and in BAL fluid obtained from mild (n = 11) and moderate (n = 14) allergic asthmatic and non-asthmatic control (n = 10) subjects pre and post in vivo rhinovirus infection. BAL cells produced significantly greater levels of fractalkine than PBMCs. Rhinovirus infection increased production of fractalkine by BAL cells from non-asthmatic controls (P<0.01) and in M1-polarised macrophages (P<0.05), but not in BAL cells from mild asthmatics or in M2 polarised macrophages. Rhinovirus induced fractalkine in PBMCs from asthmatic (P<0.001) and healthy control subjects (P<0.05). Trends towards induction of fractalkine in moderate asthmatic subjects during in vivo rhinovirus infection failed to reach statistical significance. Fractalkine may be involved in both immunopathological and anti-viral immune responses to rhinovirus infection. Further investigation into how fractalkine is regulated across different cell types and into the effect of stimulation including rhinovirus infection is warranted to better understand the precise role of this unique dual adhesion factor and chemokine in immune cell recruitment.
Highlights
Rhinoviruses (RVs) are common cold viruses, associated with the majority of asthma exacerbations [1,2]
Fractalkine levels in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from asthmatic and nonasthmatic subjects To compare expression levels of fractalkine produced by non-infected cells, BAL cells and PBMCs from allergic asthmatics (n = 15) and non-asthmatics (n = 15) were incubated for 8h in media alone
BAL cells secreted greater levels of spontaneous soluble fractalkine compared to PBMCs in both non-asthmatic and asthmatic subjects (Fig 1B, P
Summary
Rhinoviruses (RVs) are common cold viruses, associated with the majority of asthma exacerbations [1,2]. Th1 and related (type 1) immune responses are vital in rhinovirus clearance and resolution of virus-induced cell damage [3]. RVs predominately infect bronchial epithelial cells and alveolar macrophages (AMs) via cellular proteins, such as intercellular adhesion molecule 1 (ICAM-1), low-density lipoprotein receptor (LDLR) or cadherin-related family member 3 (CDHR3) in a strain-dependent manner [13, 14, 15]. M1 macrophages are believed to be a major source of Th1 promoting cytokines and chemokines [18] and may be important for orchestrating clearance of RV during infection. As RV infection in asthma has been associated with propagation of type 2 inflammation [9,10,11,12], it has been proposed that there is involvement of M2 cells in this response [19]
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