GM-CSF-mediated epithelial-immune cell cross-talk orchestrates pulmonary immunity to Aspergillus fumigatus Journal Article
| Authors: | Mills, K. A. M.; Westermann, F.; Espinosa, V.; Rosiek, E.; Desai, J. V.; Aufiero, M. A.; Guo, Y.; Liu, F. L.; Mitchell, K. A.; Tuzlak, S.; De Feo, D.; Lionakis, M. S.; Rivera, A.; Becher, B.; Hohl, T. M. |
| Article Title: | GM-CSF-mediated epithelial-immune cell cross-talk orchestrates pulmonary immunity to Aspergillus fumigatus |
| Abstract: | Aspergillus fumigatus causes life-threatening mold pneumonia in immunocompromised patients, particularly in those with quantitative or qualitative defects in neutrophils. Whereas innate immune cell cross-talk licenses neutrophil antifungal activity in the lung, the role of epithelial cells in this process is unknown. Here, we find that surfactant protein C (SPC)-expressing lung epithelial cells integrate infection-induced interleukin-1 and type III interferon signaling to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) preferentially at local sites of fungal infection and neutrophil influx. Using in vivo models that distinguish the role of GM-CSF during acute infection from its homeostatic function in alveolar macrophage survival and surfactant catabolism, we demonstrate that epithelial-derived GM-CSF increases the accumulation and fungicidal activity of GM-CSF-responsive neutrophils, which is essential for host survival. Our findings establish SPC+ epithelial cells as a central player in regulating the quality and strength of neutrophil-dependent immunity against inhaled mold pathogens. |
| Keywords: | infection; neutrophils; monocytes; macrophages; antifungal activity; specificity; activation; protection; reporter; alveolar proteinosis |
| Journal Title: | Science Immunology |
| Volume: | 10 |
| Issue: | 105 |
| ISSN: | 2470-9468 |
| Publisher: | Amer Assoc Advancement Science |
| Date Published: | 2025-03-01 |
| Start Page: | eadr0547 |
| Language: | English |
| ACCESSION: | WOS:001449212300002 |
| DOI: | 10.1126/sciimmunol.adr0547 |
| PROVIDER: | wos |
| PUBMED: | 40117345 |
| PMCID: | PMC12122100 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Tobias M. Hohl -- Source: Wos |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work