Macrophage activation in response to LPS is coupled to profound metabolic changes, typified by accumulation of the TCA cycle intermediates citrate, itaconate, and succinate. We have identified that endogenous type I IFN controls the cellular citrate/α-ketoglutarate ratio and inhibits expression and activity of isocitrate dehydrogenase (IDH); and, via 13C-labeling studies, demonstrated that autocrine type I IFN controls carbon flow through IDH in LPS-activated macrophages. We also found that type I IFN–driven IL-10 contributes to inhibition of IDH activity and itaconate synthesis in LPS-stimulated macrophages. Our findings have identified the autocrine type I IFN pathway as being responsible for the inhibition of IDH in LPS-stimulated macrophages.
David P. De Souza, Adrian Achuthan, Man K.S. Lee, Katrina J. Binger, Ming-Chin Lee, Sophia Davidson, Dedreia L. Tull, Malcolm J. McConville, Andrew D. Cook, Andrew J. Murphy, John A. Hamilton, Andrew J. Fleetwood
Usage data is cumulative from September 2019 through February 2020.
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.