| First Author | Li DD | Year | 2022 |
| Journal | Cell Host Microbe | Volume | 30 |
| Issue | 4 | Pages | 530-544.e6 |
| PubMed ID | 35316647 | Mgi Jnum | J:337392 |
| Mgi Id | MGI:7286265 | Doi | 10.1016/j.chom.2022.02.017 |
| Citation | Li DD, et al. (2022) Fungal sensing enhances neutrophil metabolic fitness by regulating antifungal Glut1 activity. Cell Host Microbe 30(4):530-544.e6 |
| abstractText | Combating fungal pathogens poses metabolic challenges for neutrophils, key innate cells in anti-Candida albicans immunity, yet how host-pathogen interactions cause remodeling of the neutrophil metabolism is unclear. We show that neutrophils mediate renal immunity to disseminated candidiasis by upregulating glucose uptake via selective expression of glucose transporter 1 (Glut1). Mechanistically, dectin-1-mediated recognition of beta-glucan leads to activation of PKCdelta, which triggers phosphorylation, localization, and early glucose transport by a pool of pre-formed Glut1 in neutrophils. These events are followed by increased Glut1 gene transcription, leading to more sustained Glut1 accumulation, which is also dependent on the beta-glucan/dectin-1/CARD9 axis. Card9-deficient neutrophils show diminished glucose incorporation in candidiasis. Neutrophil-specific Glut1-ablated mice exhibit increased mortality in candidiasis caused by compromised neutrophil phagocytosis, reactive oxygen species (ROS), and neutrophil extracellular trap (NET) formation. In human neutrophils, beta-glucan triggers metabolic remodeling and enhances candidacidal function. Our data show that the host-pathogen interface increases glycolytic activity in neutrophils by regulating Glut1 expression, localization, and function. |
