Listeria monocytogenes infection induces prosurvival metabolic signaling in macrophages
Program in Gene Function and Expression; Department of Molecular Genetics and Microbiology
Medical Subject Headings
Animals; Apoptosis Regulatory Proteins; Blotting, Western; Female; Gene Expression; Gene Expression Regulation; In Situ Nick-End Labeling; Listeria monocytogenes; Listeriosis; Macrophages; Mice; Mice, Inbred C57BL; Receptors, Immunologic; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Steroid Hydroxylases; Up-Regulation
Genetics and Genomics
Host cells use metabolic signaling through the LXRalpha nuclear receptor to defend against Listeria monocytogenes infection. 25-Hydroxycholesterol is a natural ligand of LXRs that is produced by the enzyme cholesterol 25-hydroxylase (CH25H). We found that expression of Ch25h is upregulated following L. monocytogenes infection in a beta interferon (IFN-beta)-dependent fashion. Moreover, increased Ch25h expression promotes survival of L. monocytogenes-infected cells and increases sensitivity of the host to infection. We determined that expression of Cd5l, a prosurvival gene, is controlled by CH25H. In addition, we found that CD5L inhibits activation of caspase-1, promoting survival of infected macrophages. Our results reveal a mechanism by which an intracellular pathogen can prolong survival of infected cells, thus providing itself with a protected environment in which to replicate.
Rights and Permissions
Citation: Infect Immun. 2011 Apr;79(4):1526-35. Epub 2011 Jan 24. Link to article on publisher's site