Homeostatic inflammation in innate immunity

• Pathogen sensors respond not only to pathogens but also to self-derived products.
• The self-derived products are metabolites such as fatty acids or nucleic acids.
• The metabolites activate sensors to lead to the homeostatic inflammation.
• Endolysosome is a crucial intracellular platform for the homeostatic inflammation.
• Dendritic cells lead to the homeostatic inflammation in a subset-specific way.

Innate immune sensors respond not only to microbial products but also to endogenous metabolites such as nucleic acids (NAs) and lipids. Toll-like receptors (TLRs) deliver a signal from the plasma membrane and also from endolysosomes, where NAs and lipids are catabolized. Interaction of TLRs with metabolites in endolysosomes leads to homeostatic TLR activation. Dendritic cells expressing NA-sensing TLRs are steadily activated by metabolites derived from the host or commensals and produce type I IFNs, thereby provoking various types of inflammatory conditions. Here, we discuss how homeostatic inflammation is induced by innate immune sensors and is involved in maintaining immune homeostasis and causing non-infectious inflammatory diseases.

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