Novel pathways of self- and cross-tolerance in monocytes

In this issue of Blood, Freise et al1 describe novel pathways responsible for self- and cross-tolerance of monocytes evoked by endotoxin stimulation or by endogenous Toll-like receptor 4 (TLR4) ligands (see figure). This study helps unravel the pathways of innate immune memory of monocyte hyporesponsiveness (see figure), which occur in systemic inflammatory response syndrome (SIRS) and contribute to development of secondary infections and severe sepsis.