Role of granulocyte-macrophage colony-stimulating factor signaling in regulating neutrophil antifungal activity and the oxidative burst during respiratory fungal challenge Journal Article


Authors: Kasahara, S.; Jhingran, A.; Dhingra, S.; Salem, A.; Cramer, R. A.; Hohl, T. M.
Article Title: Role of granulocyte-macrophage colony-stimulating factor signaling in regulating neutrophil antifungal activity and the oxidative burst during respiratory fungal challenge
Abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that plays a critical role in regulating myeloid cell host defense. In this study, we demonstrated that GM-CSF signaling plays an essential role in antifungal defense against Aspergillus fumigatus. Mice that lack the GM-CSF receptor β chain (GM-CSFRβ) developed invasive hyphal growth and exhibited impaired survival after pulmonary challenge with A. Fumigatus conidia. GM-CSFRβ signaling regulated the recruitment of inflammatory monocytes to infected lungs, but not the recruitment of effector neutrophils. Cell-intrinsic GM-CSFRβ signaling mediated neutrophil and inflammatory monocyte antifungal activity, because lung GM-CSFRβ-/- leukocytes exhibited impaired conidial killing compared with GM-CSFRβ+/+ counterparts in mixed bone marrow chimeric mice. GM-CSFRβ-/- neutrophils exhibited reduced (hydrogenated) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in vivo. Conversely, administration of recombinant GM-CSF enhanced neutrophil NADPH oxidase function, conidiacidal activity, and lung fungal clearance in A. Fumigatus-challenged mice. Thus, our study illustrates the functional role of GM-CSFRβ signaling on lung myeloid cell responses against inhaled A. Fumigatus conidia and demonstrates a benefit for systemic GM-CSF administration. © 2015 The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Keywords: neutrophils; monocytes; aspergillus; gm-csf; ros
Journal Title: Journal of Infectious Diseases
Volume: 213
Issue: 8
ISSN: 0022-1899
Publisher: Oxford University Press  
Date Published: 2016-04-15
Start Page: 1289
End Page: 1298
Language: English
DOI: 10.1093/infdis/jiw054
PROVIDER: scopus
PMCID: PMC4799674
PUBMED: 26908736
DOI/URL:
Notes: Article -- Export Date: 2 June 2016 -- Source: Scopus
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MSK Authors
  1. Tobias Martin Hohl
    76 Hohl
  2. Anand   Salem
    1 Salem