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Immunomodulatory function of chitosan is dependent on complement receptor 3.

Jeanette Wagener1, Xiaowen Wang2,3, Katharina L Becker2

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Cell Surface (Amsterdam, Netherlands)
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Mammalian immune cells recognize fungal chitosan via the CR3 receptor, triggering pro-inflammatory cytokine release. This interaction activates both innate and adaptive immunity against human fungal pathogens.

Keywords:
Cell wallChitosanFungal immunologyPattern recognition receptor

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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.