Eosinophil CD48 interactions with Candida albicans Als6 is protective in vitro and in mouse systemic candidiasis

Ilan Zaffran, Pratibha Gaur, Prince Ofori, Yoav Charpak-Amikam, Hadas Pahima, David Shasha, Nir Osherov, Bernhard Hube, Ronen Ben-Ami, Julian R. Naglik, Ofer Mandelboim, Joana Vitte and Francesca Levi-Schaffer ()
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Ilan Zaffran: Hebrew University of Jerusalem
Pratibha Gaur: Hebrew University of Jerusalem
Prince Ofori: Hebrew University of Jerusalem
Yoav Charpak-Amikam: Hebrew University Medical School
Hadas Pahima: Hebrew University of Jerusalem
David Shasha: Tel-Aviv University
Nir Osherov: Tel-Aviv University
Bernhard Hube: Leibniz Institute for Natural Product Research and Infection Biology – Hans Knoell Institute
Ronen Ben-Ami: Tel-Aviv University
Julian R. Naglik: King’s College London
Ofer Mandelboim: Hebrew University Medical School
Joana Vitte: Hebrew University of Jerusalem
Francesca Levi-Schaffer: Hebrew University of Jerusalem

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Eosinophils are innate immune cells with central roles in allergy, parasitic diseases and multiple inflammatory conditions. Moreover, their role in host-pathogen interactions has been well characterized. However, the role of eosinophils during fungal infection is poorly defined. In this study, we delineate the importance of eosinophils during C. albicans systemic infections. C. albicans is promptly phagocytosed by human eosinophils, but growing hyphae escape this mechanism by releasing the fungal toxin candidalysin, which causes eosinophil membrane damage and cell death. Concomitantly, eosinophil mediators, notably major basic protein 1 (MBP-1), released during cytolysis, inhibits C. albicans growth and viability. Moreover, systemic candidiasis in genetic (Δdbl/GATA) or anti–IL-5–mediated depletion of eosinophils results in increased fungal burden and decreased survival. We here identified CD48 as a major receptor of eosinophils and possibly of other immune cells involved in the recognition of C. albicans via agglutinin-like sequence 6 (Als6). CD48 is important for protection in a model of systemic candidiasis as shown in CD48−/− mice and it binds clinical isolates of C. albicans. In conclusion, we have defined a protective role for eosinophils in vitro and in mouse C. albicans infections through CD48/Als6 host-pathogen interaction axis.

Date: 2025
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DOI: 10.1038/s41467-025-64276-3

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