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Role of Granulocyte-Macrophage Colony-Stimulating Factor Signaling in Regulating Neutrophil Antifungal Activity and the Oxidative Burst During Respiratory Fungal Challenge
by
Salem, Anand
, Kasahara, Shinji
, Jhingran, Anupam
, Dhingra, Sourabh
, Cramer, Robert A.
, Hohl, Tobias M.
in
Animals
/ Antifungal Agents - immunology
/ Aspergillosis - immunology
/ Aspergillosis - metabolism
/ Aspergillus fumigatus
/ Aspergillus fumigatus - immunology
/ Cells, Cultured
/ Flow Cytometry
/ FUNGI
/ Granulocyte-Macrophage Colony-Stimulating Factor - immunology
/ Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
/ Major and Brief Reports
/ Mice
/ Monocytes - immunology
/ Monocytes - metabolism
/ Neutrophil Activation
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Reactive Oxygen Species - immunology
/ Respiratory Burst - immunology
/ Signal Transduction - immunology
2016
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Role of Granulocyte-Macrophage Colony-Stimulating Factor Signaling in Regulating Neutrophil Antifungal Activity and the Oxidative Burst During Respiratory Fungal Challenge
by
Salem, Anand
, Kasahara, Shinji
, Jhingran, Anupam
, Dhingra, Sourabh
, Cramer, Robert A.
, Hohl, Tobias M.
in
Animals
/ Antifungal Agents - immunology
/ Aspergillosis - immunology
/ Aspergillosis - metabolism
/ Aspergillus fumigatus
/ Aspergillus fumigatus - immunology
/ Cells, Cultured
/ Flow Cytometry
/ FUNGI
/ Granulocyte-Macrophage Colony-Stimulating Factor - immunology
/ Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
/ Major and Brief Reports
/ Mice
/ Monocytes - immunology
/ Monocytes - metabolism
/ Neutrophil Activation
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Reactive Oxygen Species - immunology
/ Respiratory Burst - immunology
/ Signal Transduction - immunology
2016
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Role of Granulocyte-Macrophage Colony-Stimulating Factor Signaling in Regulating Neutrophil Antifungal Activity and the Oxidative Burst During Respiratory Fungal Challenge
by
Salem, Anand
, Kasahara, Shinji
, Jhingran, Anupam
, Dhingra, Sourabh
, Cramer, Robert A.
, Hohl, Tobias M.
in
Animals
/ Antifungal Agents - immunology
/ Aspergillosis - immunology
/ Aspergillosis - metabolism
/ Aspergillus fumigatus
/ Aspergillus fumigatus - immunology
/ Cells, Cultured
/ Flow Cytometry
/ FUNGI
/ Granulocyte-Macrophage Colony-Stimulating Factor - immunology
/ Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
/ Major and Brief Reports
/ Mice
/ Monocytes - immunology
/ Monocytes - metabolism
/ Neutrophil Activation
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Reactive Oxygen Species - immunology
/ Respiratory Burst - immunology
/ Signal Transduction - immunology
2016
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Role of Granulocyte-Macrophage Colony-Stimulating Factor Signaling in Regulating Neutrophil Antifungal Activity and the Oxidative Burst During Respiratory Fungal Challenge
Journal Article
Role of Granulocyte-Macrophage Colony-Stimulating Factor Signaling in Regulating Neutrophil Antifungal Activity and the Oxidative Burst During Respiratory Fungal Challenge
2016
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Overview
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.
Publisher
Oxford University Press
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