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Eosinophil CD48 interactions with Candida albicans Als6 is protective in vitro and in mouse systemic candidiasis
Ilan Zaffran1, Pratibha Gaur1, Prince Ofori1
1Pharmacology and Experimental Therapeutics Unit, School of Pharmacy, Institute for Drug Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
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.
Insights
Eosinophils protect against Candida albicans infections by releasing mediators that inhibit fungal growth. This study reveals the CD48/Als6 interaction is crucial for eosinophil-mediated defense.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Eosinophils are key innate immune cells involved in allergies and parasitic infections.
- Their function in fungal infections, particularly systemic candidiasis, remains poorly understood.
- Candida albicans is a common fungal pathogen causing opportunistic infections.
Purpose of the Study:
- To investigate the role of eosinophils in systemic Candida albicans infections.
- To identify host-pathogen interactions mediating eosinophil responses to C. albicans.
- To determine the protective capacity of eosinophils in a murine model of candidiasis.
Main Methods:
- In vitro assays using human eosinophils and C. albicans.
- Genetic depletion (Δdbl/GATA) and antibody-mediated depletion (anti-IL-5) of eosinophils in mice.
- Assessment of fungal burden, survival rates, and host-pathogen interactions (CD48/Als6).
Main Results:
- Eosinophils phagocytose C. albicans, but hyphae release candidalysin, causing eosinophil death.
- Eosinophil mediators, like major basic protein 1 (MBP-1), inhibit C. albicans growth.
- Eosinophil-deficient mice showed increased fungal burden and reduced survival.
- CD48 was identified as a key eosinophil receptor for C. albicans via Als6.
Conclusions:
- Eosinophils play a protective role in systemic C. albicans infections.
- The CD48/Als6 interaction is a critical axis for eosinophil-mediated immunity against C. albicans.
- Targeting this axis could offer therapeutic strategies for invasive fungal infections.
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