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Listeria monocytogenes Infection Induces Prosurvival Metabolic Signaling in Macrophages

Author:
Zou, Tie, Garifulin, Oleg, Berland, Robert, Boyartchuk, Victor L.
Source:
Infection and immunity 2011 v.79 no.4 pp. 1526-1535
ISSN:
0019-9567
Subject:
Listeria monocytogenes, caspase-1, cholesterol, genes, interferon-beta, macrophages, pathogens
Abstract:
Host cells use metabolic signaling through the LXRα 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-β)-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.
Agid:
290655