Trained Innate Immunity and Its Implications for Mucosal Immunity and Inflammation

Area of Science:

• Immunology
• Innate Immunity
• Immunological Memory

Background:

• The adaptive immune system was traditionally considered the sole possessor of immunological memory.
• Emerging evidence indicates that innate immunity can also develop memory, a phenomenon termed immunological imprinting.
• This imprinting manifests as trained immunity or tolerance, altering responses to secondary stimuli.

Purpose of the Study:

• To review the evidence for trained innate immunity across diverse organisms.
• To explore the mechanistic basis of trained immunity, including metabolic and epigenetic adaptations.
• To discuss the translational implications of trained immunity in health and disease.

Main Methods:

• Review of existing scientific literature on innate immune memory.
• Analysis of studies demonstrating trained immunity in various species, from lower organisms to humans.
• Examination of molecular and cellular mechanisms underlying trained immunity.

Main Results:

• Trained immunity involves metabolic and epigenetic reprogramming of innate immune cells and bone marrow progenitors.
• This reprogramming enhances cellular responses to subsequent challenges, even from different pathogens.
• Tolerance, another form of innate immune memory, leads to attenuated responses.

Conclusions:

• Trained immunity is an evolutionarily conserved mechanism that can protect against reinfections.
• In chronic inflammatory conditions, trained immunity may contribute to maladaptive responses and disease pathology.
• Therapeutic modulation of innate immune memory holds promise for treating infections, managing myelosuppression, and controlling inflammatory/autoimmune diseases.