DAMP sensing and sterile inflammation: intracellular, intercellular and inter-organ pathways

Damage-associated molecular patterns (DAMPs) are endogenous molecules that are released from host cells as a result of cell death or damage. The release of DAMPs in tissues is associated with loss of tissue homeostasis. Sensing of DAMPs by innate immune receptors triggers inflammation, which can be beneficial in initiating the processes that restore tissue homeostasis but can also drive inflammatory diseases. In recent years, the sensing of intracellular DAMPs has received extensive attention in the field of sterile inflammation. However, emerging studies have shown that DAMPs that originate from neighbouring cells, and even from distal tissues or organs, also mediate sterile inflammatory responses. This multi-level sensing of DAMPs is crucial for intercellular, trans-tissue and trans-organ communication. Here, we summarize how DAMP-sensing receptors detect DAMPs from intracellular, intercellular or distal tissue and organ sources to mediate sterile inflammation. We also discuss the possibility of targeting DAMPs or their corresponding receptors to treat inflammatory diseases. Here, Rongbin Zhou and colleagues review the different types of damage-associated molecular pattern (DAMP) that trigger sterile inflammation via pattern recognition receptors. The authors group these DAMPs on the basis of whether they arise from inside cells, from neighbouring cells or from distant tissues, and they discuss the relevance of such DAMPs in various inflammatory disease settings.