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The C-type lectin receptor Dcir (Clec4a2) restrains Aspergillus fumigatus elimination by limiting the degranulatory activity of neutrophils

Summary

This study reveals that a receptor called Dcir on immune cells called neutrophils actually prevents effective killing of the fungus Aspergillus fumigatus by limiting the release of antibacterial granules. When researchers removed Dcir from mice, their neutrophils became more effective at fighting the fungal infection. This suggests that blocking Dcir might help patients with fungal respiratory infections clear the pathogen more effectively.

Background

C-type lectin receptors (CLRs) are innate immune sensors crucial for antifungal defense. Dendritic cell immunoreceptor (Dcir) is an immunoregulatory CLR that limits inflammation and autoimmunity, but its role in fungal infections has not been established.

Objective

To investigate the involvement of Dcir in host defense against Aspergillus fumigatus and determine the mechanisms by which this receptor modulates the antifungal immune response in a pulmonary aspergillosis model.

Results

Dcir-deficient mice showed improved clearance of A. fumigatus from lungs without increased inflammation. Dcir-deficient neutrophils exhibited enhanced killing of A. fumigatus hyphae through increased degranulatory activity triggered by intracellular Ca2+ mobilization and PLCγ2 phosphorylation. Inhibition of neutrophil degranulation abolished the protective effect of Dcir deficiency.

Conclusion

Dcir is a novel fungal sensor that uniquely restrains rather than promotes antifungal responses by dampening neutrophil degranulation. This reveals an immunomodulatory function for Dcir in fine-tuning host effector responses and maintaining immune homeostasis during fungal infection.
  • Published in:Frontiers in Immunology,
  • Study Type:Experimental Animal Study,
  • Source: PMID: 40831560, DOI: 10.3389/fimmu.2025.1639400
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