29 Oct Not Just in Allergic Reactions: Eosinophils May Play Role in Fighting Candida Infections

MedicalResearch.com Interview with:
Prof. Francesca Levi-Schaffer and
Ilan Zaffran, PhD candidate
School of Pharmacy at the Hebrew University.

MedicalResearch.com: What is the background for this study? Does this function of eosinophils use a different mechanism from their role in allergic reactions?

Response: Eosinophils are best known as effector cells in allergic diseases such as asthma, but they are in fact multifunctional immune cells involved in host defense and homeostasis. In recent years, researchers have begun to explore how eosinophils interact with microbes and viruses, and even with fungal allergens. However, until now, no study had investigated the role of eosinophils in defense against pathogenic fungi such as Candida albicans.

Eosinophils attacking C. albicans | Credit: Ilan Zaffran

Our work is the first to show that eosinophils can directly recognize and respond to this common opportunistic fungus. While the underlying mechanisms such as degranulation and cytokine release are fundamentally similar to those used during allergic responses, in this context they serve a protective antifungal role, expanding the known functional spectrum of eosinophils beyond allergy. 

In addition, we discovered that eosinophils use the surface receptor CD48 to directly recognize the fungal adhesin Als6 on Candida albicans.

MedicalResearch.com: What are the main findings?

Response:  We demonstrated that the interaction between eosinophil CD48 and the fungal ligand Als6 triggers antifungal activity. This includes eosinophil activation, degranulation, and fungal killing both in vitro and in a mouse model of systemic candidiasis.
Mice deficient in eosinophils or in CD48 signaling were more susceptible to fungal infection, highlighting the protective role of eosinophils in systemic candidiasis. 

MedicalResearch.com: What should readers take away from your report?

Response: Our work reveals that eosinophils are not only pro-inflammatory cells involved in allergic reactions but also key players in antifungal immunity.
By identifying a specific receptor–ligand interaction (CD48–Als6), we open the way to new therapeutic targets that could enhance antifungal defense or modulate eosinophil activity in different disease contexts.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: We are aware of the limitations of our study, particularly the lack of evidence from human patients treated with eosinophil-depleting biological drugs (mepolizumab, reslizumab, and benralizumab), which would help confirm the relevance of our findings in clinical settings. Nevertheless, future studies should explore whether similar eosinophil–pathogen recognition mechanisms exist for other fungi or microbes, and whether modulation of CD48 activity could be harnessed therapeutically.

It will also be important to define how eosinophil antifungal functions are regulated in human tissues during infection, and how they might influence the development of diseases where eosinophils and Candida are both present—such as colon cancer, inflammatory bowel disease (IBD), atopic dermatitis, asthma, and eosinophilic esophagitis (EoE).

No disclosures to declare.

Citation:

Zaffran, I., Gaur, P., Ofori, P. et al. Eosinophil CD48 interactions with Candida albicans Als6 is protective in vitro and in mouse systemic candidiasis. Nat Commun 16, 9291 (2025). https://doi.org/10.1038/s41467-025-64276-3

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Last Updated on October 29, 2025 by Marie Benz MD FAAD