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GM-CSF treatment prevents respiratory syncytial virus– induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation

Thomas Naessens (UGent) , Bert Schepens (UGent) , Muriel Smet (UGent) , Charlotte Pollard (UGent) , Lien Van Hoecke (UGent) , Ans De Beuckelaer (UGent) , Monique Willart (UGent) , Bart Lambrecht (UGent) , Stefaan De Koker (UGent) , Xavier Saelens (UGent) , et al.
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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 CD11chi 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 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.
Keywords
INTERLEUKIN-4, IMMUNE, CELLS, ASTHMA, alveolar macrophage, GM-CSF, ALLERGIC AIRWAY INFLAMMATION, MUCOSAL SENSITIZATION, CYTOKINE SECRETION, LUNG INFLAMMATION, MURINE MODEL, INFECTION, Allergic asthma, respiratory syncytial virus-induced exacerbation

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Chicago
Naessens, Thomas, Bert Schepens, Muriel Smet, Charlotte Pollard, Lien Van Hoecke, Ans De Beuckelaer, Monique Willart, et al. 2016. “GM-CSF Treatment Prevents Respiratory Syncytial Virus– Induced Pulmonary Exacerbation Responses in Postallergic Mice by Stimulating Alveolar Macrophage Maturation.” Journal of Allergy and Clinical Immunology 137 (3): 700–709.
APA
Naessens, T., Schepens, B., Smet, M., Pollard, C., Van Hoecke, L., De Beuckelaer, A., Willart, M., et al. (2016). GM-CSF treatment prevents respiratory syncytial virus– induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 137(3), 700–709.
Vancouver
1.
Naessens T, Schepens B, Smet M, Pollard C, Van Hoecke L, De Beuckelaer A, et al. GM-CSF treatment prevents respiratory syncytial virus– induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 2016;137(3):700–9.
MLA
Naessens, Thomas, Bert Schepens, Muriel Smet, et al. “GM-CSF Treatment Prevents Respiratory Syncytial Virus– Induced Pulmonary Exacerbation Responses in Postallergic Mice by Stimulating Alveolar Macrophage Maturation.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 137.3 (2016): 700–709. Print.
@article{7040212,
  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 CD11chi 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 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.},
  author       = {Naessens, Thomas and Schepens, Bert and Smet, Muriel and Pollard, Charlotte and Van Hoecke, Lien and De Beuckelaer, Ans and Willart, Monique and Lambrecht, Bart and De Koker, Stefaan and Saelens, Xavier and Grooten, Johan},
  issn         = {1173-2563},
  journal      = {JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY},
  language     = {eng},
  number       = {3},
  pages        = {700--709},
  title        = {GM-CSF treatment prevents respiratory syncytial virus-- induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation},
  url          = {http://dx.doi.org/10.1016/j.jaci.2015.09.031},
  volume       = {137},
  year         = {2016},
}

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