Induction of Innate Immune Memory in LPS-Primed Microglial Cells by Water-Soluble Chitosan.

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Innate immune memory, or trained immunity, involves long-lasting innate immune cell responses to pathogens.
• This phenomenon is driven by epigenetic modifications, altered intracellular signaling, and cellular metabolism.
• Understanding the molecular mechanisms of innate memory induction is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the effect of water-soluble chitosan on inducing trained immunity in microglial cells.
• To analyze the molecular basis of chitosan-induced innate immune memory.
• To evaluate chitosan's potential as a novel therapeutic agent for modulating innate immunity.

Main Methods:

• Microglial cells were primed with lipopolysaccharide (LPS) and treated with water-soluble chitosan.
• Trained immune responses were assessed by measuring proinflammatory markers (e.g., iNOS, cytokines).
• Metabolic changes (lactate production) and epigenetic modifications were analyzed.

Main Results:

• LPS stimulation alone induced immune tolerance, reducing iNOS and proinflammatory cytokines.
• Chitosan treatment induced long-lasting memory microglial cells with high iNOS levels and increased lactate production.
• Chitosan treatment led to epigenetic modifications and upregulated proinflammatory cytokines upon restimulation.

Conclusions:

• Water-soluble chitosan effectively induces microglial-trained immunity.
• Chitosan targets distinct epigenetic and metabolic pathways to establish this memory-like response.
• Chitosan represents a promising therapeutic approach for modulating innate immunity via trained immunity in vitro.