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GM-CSF treatment prevents respiratory syncytial virusU+2013 induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation

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Background: Human respiratory syncytial virus (RSV) is a frequent cause of asthma exacerbations, yet the susceptibility of asthmatic patients to RSV is poorly understood.Objective: We sought to address the contribution of resident alveolar macrophages (rAMs) to susceptibility to RSV infection in mice that recovered from allergic airway eosinophilia.Methods: Mice were infected with RSV virus after clearance of allergic airway inflammation (AAI). The contribution of post-AAI rAMs was studied in vivo by means of clodronate liposomeU+2013mediated depletion, adoptive transfer, and treatment with recombinant cytokines before RSV infection.Results: After clearing the allergic bronchial inflammation, post-AAI mice had bronchial hyperreactivity and increased inflammatory cell influx when infected with RSV compared with nonallergic mice, whereas viral clearance was comparable in both mouse groups. Post-AAI rAMs were necessary and sufficient for mediating these proinflammatory effects. In post-AAI mice the residing CD11chi autofluorescent rAM population did not upregulate the terminal differentiation marker sialic acidU+2013binding immunoglobulin-like lectin F and overproduced TNF and IL-6 through increased nuclear factor kB nuclear translocation. In line with these results, post-AAI lungs had reduced levels of the rAM maturation cytokine GM-CSF. Intratracheal administration of GM-CSF induced final rAM maturation in post-AAI mice and prevented the increased susceptibility to RSV-induced hyperreactivity and inflammation.
Tijdschrift: Clinical Drug Investigation
ISSN: 1173-2563
Issue: 3
Volume: 137
Pagina's: 700 - 709
Jaar van publicatie:2016