Training vs. Tolerance: The Yin/Yang of the Innate Immune System

Area of Science:

• Immunology
• Cellular Biology
• Epigenetics

Background:

• Traditionally, immune memory was solely linked to acquired immune cells.
• Recent research highlights memory-like features in innate immune cells, termed trained immunity.
• Endotoxin tolerance represents an immunosuppressive state in myeloid cells, reducing inflammatory capacity.

Purpose of the Study:

• To review the opposing mechanisms of trained immunity and endotoxin tolerance in innate and non-immune cells.
• To describe the molecular, metabolic, and epigenetic underpinnings of these processes.
• To interpret the clinical relevance of trained immunity and endotoxin tolerance in inflammatory pathologies.

Main Methods:

• Review of existing scientific literature on trained immunity and endotoxin tolerance.
• Analysis of molecular, metabolic, and epigenetic alterations in immune cells.
• Correlation of cellular responses with clinical implications in inflammatory diseases.

Main Results:

• Trained immunity enhances responsiveness to subsequent challenges, offering protection against infections.
• Endotoxin tolerance reduces inflammation, promoting cellular repair mechanisms.
• Dysregulation of these adaptive processes can lead to maladaptive effects, such as increased infection susceptibility or inflammatory disorder progression.

Conclusions:

• Trained immunity and endotoxin tolerance are adaptive features of innate immunity with distinct outcomes.
• Epigenetic and metabolic reprogramming are central to both phenomena.
• Understanding these mechanisms is crucial for managing inflammatory diseases.