A novel complement-metabolism-inflammasome axis as a key regulator of immune cell effector function

The inflammasomes are intracellular multiprotein complexes that induce and regulate the generation of the key pro-inflammatory cytokines IL-1 beta and IL-18 in response to infectious microbes and cellular stress. The activation of inflammasomes involves several upstream signals including classic pattern or danger recognition systems such as the TLRs. Recently, however, the activation of complement receptors, such as the anaphylatoxin C3a and C5a receptors and the complement regulator CD46, in conjunction with the sensing of cell metabolic changes, for instance increased amino acid influx and glycolysis (via mTORC1), have emerged as additional critical activators of the inflammasome. This review summarizes recent advances in our knowledge about complement-mediated inflammasome activation, with a specific focus on a novel complement - metabolism - NLRP3 inflammasome axis.