Metabolic basis of trained immunity| Biomed Grid

Innate immunity is considered to be unable to construct immunological memory in the traditional concept. However, in recent years, there is growing evidence to dispute this idea. Plants and invertebrates lacking an adaptive immune system can mount resistance to secondary infections [1,2]. NK cells and monocytes are also found have memory characteristics [3,4] In 2011, Netea et al. [5] proposed a new term “trained immunity” for describing innate immune memory responses. In 2012, Quintin et al. [6] further demonstrate trained immunity even occurred in mice lacking T and B cells, serving as an increased response to secondary infections which is monocyte- dependent after priming with β-glucan from Candida albicans. Further molecular mechanisms studies of trained immunity suggest that epigenetic reprogramming plays a key role in mediating innate immune memory. Quintin et al. [6] demonstrated that β-glucans from C. albicans cell wall induced monocyte training associated with epigenetic changes in H3K4me3, which requires receptor dectin-1 and the non-canonical Raf-1 pathway. Another work demonstrated that BCG (bacille calmette guerin) has similar trained immunity inducing function through the NOD2 receptor and also mediated by increased H3K4me3 [7]. Ostuni et al. [8] suggested that latent enhancers, a group of stimulus-specific expanded cis-regulatory repertoire associated with a steady H3K4me1 mark could provide an epigenomic memory of the exposure to environmental agents. This new founding may further describe the mechanisms of trained immunity. However, there is poorly insight on the specific cellular processes that mediate trained immunity. Recently, glucose metabolism switch from oxidative phosphorylation to aerobic glycolysis has turned out to be crucial for activation of immune cells [9]. There is a growing concern over metabolism switch and innate host defense.