Inhaled GM-CSF in neonatal mice provides durable protection against bacterial pneumonia

Pneumonia poses profound health threats to preterm infants. Alveolar macrophages (AMs) eliminate inhaled pathogens while maintaining surfactant homeostasis. As AM development only occurs perinatally, therapies that accelerate AM maturation in preterms may improve outcomes. We tested therapeutic resc...

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Bibliographic Details
Published in:Science advances 2019-08, Vol.5 (8), p.eaax3387-eaax3387
Main Authors: Todd, Elizabeth M, Ramani, Rashmi, Szasz, Taylor P, Morley, S Celeste
Format: Article
Language:English
Subjects:
Administration, Inhalation
Animals
Animals, Newborn
Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Humans
Immunology
Macrophages, Alveolar - cytology
Macrophages, Alveolar - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Microfilament Proteins - genetics
Pneumonia, Bacterial - immunology
Pneumonia, Bacterial - microbiology
Pneumonia, Bacterial - prevention & control
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Summary:Pneumonia poses profound health threats to preterm infants. Alveolar macrophages (AMs) eliminate inhaled pathogens while maintaining surfactant homeostasis. As AM development only occurs perinatally, therapies that accelerate AM maturation in preterms may improve outcomes. We tested therapeutic rescue of AM development in mice lacking the actin-bundling protein L-plastin (LPL), which exhibit impaired AM development and increased susceptibility to pneumococcal lung infection. Airway administration of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) to LPL neonates augmented AM production. Airway administration distinguishes the delivery route from prior human infant trials. Adult LPL animals that received neonatal GM-CSF were protected from experimental pneumococcal challenge. No detrimental effects on surfactant metabolism or alveolarization were observed. Airway recombinant GM-CSF administration thus shows therapeutic promise to accelerate neonatal pulmonary immunity, protecting against bacterial pneumonia.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.aax3387