Culprits with evolutionary ties

Abstract

The cellular organelles we know as mitochondria are thought to have originated as symbiotic bacteria. Indeed, the two use common mechanisms to trigger innate immune responses to injury and infection, respectively. Mitochondria are endosymbiotic descendents of bacteria, well tolerated by the eukaryotic cells that they now serve after millions of years of co-evolution. But in extremis it seems strains in the relationship may emerge. Tests on plasma samples from patients who had suffered severe trauma show that mitochondrial DAMPs (or damage-associated molecular patterns) are released into the circulation as a result of tissue damage, where they activate neutrophils via specific formyl peptide receptors. This triggers systemic inflammation, tissue damage and apparent sepsis. These DAMPs interact with receptors that are part of the innate immune response to molecules known as PAMPs (pathogen associated molecular patterns), which are expressed on invading microorganisms, causing bacterial sepsis. This finding appears to explain the apparent sepsis sometimes associated with severe trauma even when no infection is present.