Trends in Immunology
Research updateEndogenous ligands of Toll-like receptors: implications for regulating inflammatory and immune responses
Section snippets
Necrotic cells and heat-shock proteins signal through TLRs
The two modes of cell death, broadly characterized as apoptotic or necrotic, have strikingly different pathophysiological consequences [20]. Significantly, necrotic cell death might be the primary cytotoxic mechanism following tissue injury. Although apoptotic cells are rapidly phagocytosed before lysis, necrotic cells can release their intracellular contents, which might contribute to inflammation following injury [21]. Indeed, necrotic cells, but not apoptotic cells, activate NF-κB in viable
Do endogenous TLR ligands regulate adaptive immunity?
In an alternate view of induction of an adaptive immune response, Matzinger proposed the ‘danger’ model. This model proposes that the immune system evolved to primarily recognize danger signals rather than nonself signals 35., 36.. Danger signals not only include microbial agents but also endogenous agents that can stimulate an immune response against both self and nonself antigens. This model has been proposed for the development of certain forms of autoimmunity and responses to foreign grafts
Concluding remarks
These findings indicate that both microbial and endogenous agents might signal through the same set of evolutionarily conserved receptor proteins. However, it should be reiterated that it has not been unequivocally demonstrated, especially in the case of HSPs, that microbial contamination is not a contributing factor in studies of endogenous agents. A key question for future investigations is the physiological nature of responses triggered following engagement of TLRs by endogenous ligands. Is
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