Maladaptive trained immunity in viral infections

Area of Science:

• Immunology
• Cellular Biology
• Epigenetics

Background:

• Trained immunity (TRIM) involves long-lasting functional reprogramming of innate immune cells.
• Initially observed in myeloid cells, TRIM is now recognized in nonmyeloid cells like endothelial and glial cells.
• TRIM can be protective against infections but also maladaptive, driving chronic inflammation and disease.

Purpose of the Study:

• To review virus-induced trained immunity.
• To explore microbial, metabolic, and endogenous inducers of TRIM.
• To discuss factors contributing to maladaptive TRIM and its role in systemic diseases.

Main Methods:

• Examination of TRIM-initiating ligands and receptors.
• Dissection of associated signaling and epigenetic pathways.
• Review of TRIM induction in bone marrow and involvement of various cell types.

Main Results:

• Maladaptive TRIM arises from contextual factors (stimulus persistence, dose, microenvironment, inflammation) rather than specific molecular events.
• The nature of secondary challenges influences whether TRIM responses are adaptive or maladaptive.
• TRIM involves lipid rafts for sustained memory-like behavior.

Conclusions:

• Maladaptive TRIM contributes to systemic diseases including atherosclerosis, diabetes, sepsis, cancer, and autoimmunity.
• TRIM influences viral vaccine responses.
• Strategies to redirect maladaptive TRIM and future research questions are proposed.