Immunomodulatory function of chitosan is dependent on complement receptor 3

Area of Science:

• Immunology
• Microbiology
• Biochemistry

Background:

• Chitosan, derived from chitin, is abundant in fungal cell walls.
• Mammalian immune recognition of fungal chitosan is less understood compared to plant immunity.
• Human pathogenic fungi pose significant health risks, necessitating a deeper understanding of immune responses.

Purpose of the Study:

• To investigate the mammalian immune system's recognition of chitosan from human pathogenic fungi.
• To identify the specific immune receptor involved in chitosan recognition.
• To elucidate the downstream signaling pathways and immune responses triggered by fungal chitosan.

Main Methods:

• Utilized human monocytes and macrophages expressing the CR3 receptor.
• Exposed immune cells to chitosan from various fungal species.
• Measured cytokine secretion (IL-6, IL-1β, TNF) and assessed phagocytosis.
• Investigated T-helper (Th) cell responses using fungal peptides (Aspf2) and MHCII presentation.

Main Results:

• The mammalian β-integrin CR3 complement scavenger receptor recognizes chitosan from diverse fungal sources.
• Chitosan recognition by CR3 leads to the secretion of pro-inflammatory cytokines IL-6, IL-1β, and TNF.
• Cytokine secretion was dependent on the phagocytosis of chitosan particles.
• Co-administration of chitosan with an Aspergillus fumigatus peptide (Aspf2) potentiated a Th response, inducing IL-22 production.

Conclusions:

• Fungal cell wall chitosan acts as a potent activator of the mammalian innate immune system through CR3 receptor engagement.
• Chitosan also plays a role in bridging innate and adaptive immunity by potentiating T-helper cell responses.
• Understanding chitosan-mediated immune activation is crucial for developing novel therapeutic strategies against fungal infections.