Immune responses are classically divided into innate immune responses, which react rapidly and nonspecifically upon encountering a pathogen, and adaptive immune responses, which are slower to develop but are specific and build up immunological memory.
However, the dogma that only adaptive immunity can build immunological memory has been challenged by Netea and co-workers who showed that innate immune cells can display adaptive characteristics after challenge with pathogens or their products. This de facto immunological memory has been termed ‘trained immunity’ or ‘innate immune memory’.
Trained Immunity – A paradigm shift
Mechanistic studies have demonstrated that trained immunity is based on epigenetic reprogramming, which is broadly defined as sustained changes in transcription programs and cell physiology that do not involve permanent genetic changes, such as mutations and recombination.
Histone modifications with chromatin reconfiguration have proven to be a central process for trained immunity. This leads to transcriptional programs that rewire the intracellular immune signaling increasing the innate immune cells’ capacity to respond to stimulation.
Trained immunity programs have evolved as adaptive states that enhance fitness of the host, for example protective effects after infection or vaccination, or induction of mucosal tolerance toward colonizing microorganisms.
However, when inappropriately activated, trained immunity programs can become maladaptive, as in post-sepsis immune paralysis or auto-inflammatory diseases. This opens-up a huge potential designing new therapeutic strategies through activation of trained immunity for the treatment of immune deficiency states as in sepsis or cancer, but also modulation of exaggerated inflammation in immunology-driven disorders such as atherosclerosis or rheumatoid arthritis.