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bioRxiv · 10.64898/2026.01.28.702262

Dectin-2-dependent adaptive immunity governs intestinal clearance of systemic Candida albicans

Dambuza, I. M.·Salazar, F.·Harvey, J.·Phillips-Brookes, A.·Kaplan, D. H.·Brown, G. D.
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Abstract

Effective immunity to Candida albicans requires coordination between innate recognition and induction of adaptive CD4 T cell responses. While the C-type lectin receptor Clec4n (Dectin-2) is known to drive Th17 polarization, its role in shaping tissue-specific adaptive responses remains incompletely understood. Here, we used an OT-II antigen-specific CD4 T cell transfer model combined with OVA-expressing Candida albicans to dissect the function of Dectin-2 during systemic infection. We found that Dectin-2 is dispensable for antigen presentation and CD4 T cell priming in gut-draining lymph nodes. Moreover, we show that Dectin-2-deficient mice fail to control fungal growth in the intestinal mucosa, despite elevated local production of IL-17A and GM-CSF. The increased susceptibility of the Dectin-2-deficient mice was associated with impaired neutrophil activation in the intestinal mucosa. These findings identify a tissue-specific checkpoint role for Dectin-2, linking balanced adaptive Th17 cytokine responses to granulocyte function, and revealing a previously unappreciated mechanism required for anti-fungal immune regulation at intestinal mucosal surface.

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Dambuza, I. M., Salazar, F., Harvey, J., Phillips-Brookes, A., Kaplan, D. H., Brown, G. D.. 2026-01-31. Dectin-2-dependent adaptive immunity governs intestinal clearance of systemic Candida albicans. https://doi.org/10.64898/2026.01.28.702262

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