Trained immunity: induction of an inflammatory memory in disease
Schlüter et al./Nature/2025
Why It Matters
This paper caught my attention because it explains a mechanism I've been watching: why some people seem to handle infections better after certain vaccines (like BCG), and why chronic inflammation might persist long after the original trigger is gone. The double-edged sword here is clear—trained immunity can protect you against unrelated infections, but the same mechanism can drive autoimmune disease and cardiovascular problems if it goes haywire. Understanding this helps explain why your infection history matters for current health.
Key Findings
- BCG vaccine (tuberculosis) has been inducing trained immunity for decades, providing protection against unrelated infections through epigenetic reprogramming of bone marrow progenitor cells
- Trained immunity operates through metabolic changes (shift to glycolysis) and epigenetic modifications (histone changes, DNA methylation) that persist in hematopoietic stem cells
- The same mechanism that protects against infections can backfire—inappropriate trained immunity induction drives chronic inflammation in cardiovascular disease, autoimmunity, and neurodegenerative conditions
- Trained immunity can help overcome cancer-related immunosuppression, suggesting potential therapeutic applications in oncology
- Unlike adaptive immunity (T cells, antibodies), trained immunity works through innate immune cells (monocytes, macrophages, NK cells) and doesn't require antigen specificity