Trained immunity: A program of innate immune memory in health and disease

Abstract

The general view that only adaptive immunity can build immunological memory has recently been challenged. In organisms lacking adaptive immunity as well as in mammals, the innate immune system can mount resistance to reinfection, a phenomenon termed trained immunity or innate immune memory. Trained immunity is orchestrated by epigenetic reprogramming, broadly defined as sustained changes in gene expression and cell physiology that do not involve permanent genetic changes such as mutations and recombination, which are essential for adaptive immunity. The discovery of trained immunity may open the door for novel vaccine approaches, for new therapeutic strategies for the treatment of immune deficiency states, and for modulation of exaggerated inflammation in autoinflammatory diseases.

Monocyte dysregulation and systemic inflammation during pediatric falciparum malaria

“…In contrast to tolerant monocytes, primed (or "trained") monocytes display enhanced proinflammatory cytokine production when challenged with a secondary stimulus (63). Our results are consistent with recent reports that demonstrated evidence for a priming effect on the innate immune response during P. falciparum infection.…”

Inducible epithelial resistance protects mice against leukemia-associated pneumonia

“…This broad protection bears some conceptual similarity to trained innate immunity in monocytes, macrophages, and natural killer cells. 46 However, although we observe renewed protection with repetitive Pam2-ODN treatments (ie, no tachyphylaxis), 18,27 there is not clear evidence of a memory response to subsequent pathogen challenges, defining these as distinct phenomena. Moreover, the antimicrobial response kinetics do not indicate a classical priming event.…”

'Trained immunity: consequences for lymphoid malignancies

“…Amelioration of infectious complications and hematological disease progression can be envisioned to result from the induction of trained immunity, but future studies are required to prove this exciting new hypothesis. 7 Currently, immunotherapies used for the treatment of hematological malignancies have focused on the adaptive immune system, mostly T and B lymphocyte responses. Examples are numerous and include the use of allogeneic stem cell transplantation (SCT), monoclonal antibodies, immune checkpoint inhibitors and cellular therapies (e.g., adoptive T cell transfer).…”