DIFFERENT MUTATIONS IN THE NADPH OXIDASE ENZYME LEAD TO DIFFERENT MACROPHAGE RESPONSES

Chronic granulomatous disease (CGD) is a genetic disease characterised by a dysfunctional NADPH oxidase with a reduced capacity to produce the reactive oxygen species (ROS) needed to defend against pathogens. Mutations in the various subunits of the NADPH enzyme may lead to the manifestation of CGD. In this study, we theorise that different mutations in the subunits of NADPH oxidase result in an altered macrophage response to infection.

LPS was found to decrease macrophage viability but also cause increased production of TNFa and IL-1b. The build up of dead macrophages may also contribute to the inflammatory response, characterised by TNFα and IL-1β release from the remaining active cells. PMA; used to differentiate U937 cells into macrophages, becomes cytotoxic to macrophages in a time and dose-dependent fashion. Our hypothesis that mutations in the subunits of NADPH oxidase affect the macrophage response to TLR and inflammasome response was confirmed. However, repeat experimentation and further investigations are necessary to further our understanding of the pathogenesis of CGD.

Keywords: CGD, X-linked disorders, NADPH oxidase enzyme, RNA Interference and Mutations in genes.