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  • Title: GM-CSF treatment prevents respiratory syncytial virus-induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation.
    Author: Naessens T, Schepens B, Smet M, Pollard C, Van Hoecke L, De Beuckelaer A, Willart M, Lambrecht B, De Koker S, Saelens X, Grooten J.
    Journal: J Allergy Clin Immunol; 2016 Mar; 137(3):700-9.e9. PubMed ID: 26560044.
    Abstract:
    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 liposome-mediated 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 CD11c(hi) autofluorescent rAM population did not upregulate the terminal differentiation marker sialic acid-binding immunoglobulin-like lectin F and overproduced TNF and IL-6 through increased nuclear factor κB 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. CONCLUSION: Defective production of GM-CSF leads to insufficient post-AAI rAM maturation in mice that recovered from an AAI, causing increased susceptibility to RSV-induced immunopathology. Promoting the differentiation of post-AAI rAMs might be a therapeutic option for preventing RSV-induced exacerbations in human asthmatic patients.
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