Turning on the Lights inside Neutrophils

Abstract

Cells of the innate immune compartment provide critical functions in protective responses to infec- tiousagentsaswellasinother typesofimmune responses. Responses to infections and tissue inflammation are initiated by innate cell receptors that sense conserved pathogen- and/or inflammation-derived molecular patterns and trigger functions that are critical to early control of the infection and to subsequent activation of the adaptive immune re- sponse (1, 2). Importantly, the adaptive immune response does not function in isolation, but rather guides the trafficking and function of neutrophils and macrophages to ingest and destroy bacterial and fungal pathogens. The major mechanism used by these phagocytes to destroy ingested pathogens is through the NADPH oxidase–mediated generation of reactive oxygen rad- icals and downstream mediators, including H2O2 and HOCl. The critical role of neutrophils and macrophages and their machinery in ridding the host of pathogens is best exemplified in humans who have mutations in one of the enzymatic com- ponents comprising NADPH oxidase. These mutations pre- vent the formation and/or function of the NADPH oxidase enzyme system in generating the oxidative burst and its down- stream products, so that ingested pathogens are not destroyed by the phagocytes. The resulting chronic granulomatous disease renders the afflicted individuals susceptible to chronic infec- tions that are dealt with by formation of characteristic gran- ulomas to sequester the ingested pathogens in tissue, thereby preventing their spread.