| First Author | Kasahara S | Year | 2016 |
| Journal | J Infect Dis | Volume | 213 |
| Issue | 8 | Pages | 1289-98 |
| PubMed ID | 26908736 | Mgi Jnum | J:355600 |
| Mgi Id | MGI:7750975 | Doi | 10.1093/infdis/jiw054 |
| Citation | Kasahara S, et al. (2016) Role of Granulocyte-Macrophage Colony-Stimulating Factor Signaling in Regulating Neutrophil Antifungal Activity and the Oxidative Burst During Respiratory Fungal Challenge. J Infect Dis 213(8):1289-98 |
| abstractText | 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 beta chain (GM-CSFRbeta) developed invasive hyphal growth and exhibited impaired survival after pulmonary challenge with A. fumigatus conidia. GM-CSFRbeta signaling regulated the recruitment of inflammatory monocytes to infected lungs, but not the recruitment of effector neutrophils. Cell-intrinsic GM-CSFRbeta signaling mediated neutrophil and inflammatory monocyte antifungal activity, because lung GM-CSFRbeta(-/-) leukocytes exhibited impaired conidial killing compared with GM-CSFRbeta(+/+) counterparts in mixed bone marrow chimeric mice. GM-CSFRbeta(-/-) 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-CSFRbeta signaling on lung myeloid cell responses against inhaled A. fumigatus conidia and demonstrates a benefit for systemic GM-CSF administration. |
