Immunomodulatory function of chitosan is dependent on complement receptor 3

Summary

This study reveals how the human immune system recognizes chitosan, a natural component found in the walls of disease-causing fungi like Aspergillus and Cryptococcus. Researchers discovered that immune cells use a protein called CR3 on their surface to detect and respond to chitosan by producing inflammatory chemicals that help fight infection. When chitosan works together with fungal proteins, it can boost the immune system’s response even more effectively, suggesting new ways to enhance immunity against fungal infections.

Background

Chitosan, the deacetylated form of chitin, is a significant component of fungal cell walls in species such as Aspergillus fumigatus, Cryptococcus neoformans, and Mucor species. While plant immune recognition of chitin and chitosan has been extensively studied, the mammalian immune recognition of fungal chitosan remains poorly understood.

Objective

To investigate the immunological properties of fungal chitosan and identify the pattern recognition receptors (PRRs) involved in its recognition by human immune cells, and to determine how chitosan affects both innate and adaptive immune responses.

Results

Chitosan induced significant pro-inflammatory cytokine production (IL-1β, IL-6, TNF-α) in human PBMCs in a phagocytosis-dependent manner, with intensity correlating to the degree of deacetylation. Complement receptor 3 (CR3) was identified as the crucial PRR for chitosan recognition and cytokine induction. Co-stimulation with chitosan and Aspf2 protein synergized to induce IL-22 production via CR3, particularly in approximately half of healthy donors.

Conclusion

Fungal chitosan activates both innate and adaptive immune responses through CR3-mediated recognition and phagocytosis. These findings provide important insights into immune responses against chitosan-containing fungal pathogens including Aspergillus, Cryptococcus, and Mucor species, with potential implications for understanding fungal infections and developing immunotherapeutic strategies.
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