Work

GM-CSF–mediated epithelial-immune cell cross-talk orchestrates pulmonary immunity to Aspergillus fumigatus

Year: 2025

Type: article

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.

Source: Zurich Open Repository and Archive (University of Zurich)

DOI: 10.5167/uzh-284526

Authors: Mills, Kathleen A. M., Westermann, Frederike, Espinosa, Vanessa, Rosiek, Eric, Desai, Jigar V., Aufiero, Mariano A., Guo, Yahui, Liu, Fitty L., Mitchell, Kennedy A., Tuzlak, Selma, De Feo, Donatella, Lionakis, Michail S., Rivera, Amariliz, Becher, Burkhard, Hohl, Tobias M.

Language: English

Topic: Antifungal resistance and susceptibility

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W7127571994

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