Listeria monocytogenes infection induces prosurvival metabolic signaling in macrophages.
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.
Program in Gene Function and Expression and Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Tie
T
Zou
Oleg
O
Garifulin
Robert
R
Berland
Victor L
VL
Boyartchuk
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000235:genetics; D020287:In Situ Nick-End Labeling; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000096:biosynthesis; D051116:Receptors, Scavenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013250:Steroid Hydroxylases / Q000096:biosynthesis*; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; C117272:Cd5l protein, mouse; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D013250:Steroid Hydroxylases; C507384:cholesterol 25-hydroxylase
Cell Host Microbe. 2010 May 20;7(5):412-9
20417169
Cell Struct Funct. 1991 Dec;16(6):467-74
1667507
Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16764-9
19805370
Nat Immunol. 2010 May;11(5):395-402
20351692
Biochim Biophys Acta. 1993 Feb 24;1166(2-3):177-82
8443234
J Gene Med. 2006 Jul;8(7):874-88
16718734
Proc Natl Acad Sci U S A. 1997 May 13;94(10):4895-900
9144161
Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7238-43
10377398
J Exp Med. 2006 Apr 17;203(4):933-40
16549598
Brief Funct Genomic Proteomic. 2005 Nov;4(3):258-69
16420751
Nature. 1996 Oct 24;383(6602):728-31
8878485
J Lipid Res. 2009 Nov;50(11):2258-64
19502589
Nat Immunol. 2010 Dec;11(12):1136-42
21057511
Science. 2004 Apr 9;304(5668):242-8
15073367
Nat Immunol. 2004 Sep;5(9):891-8
15311277
J Clin Invest. 2005 Feb;115(2):359-68
15650769
PLoS Genet. 2007 Sep;3(9):1587-97
17845078
J Immunol. 2008 Jun 1;180(11):7558-64
18490757
J Immunol. 2003 Jan 1;170(1):430-7
12496428
Cell Microbiol. 2007 Nov;9(11):2562-70
17714514
J Exp Med. 2004 Aug 16;200(4):527-33
15302899
J Immunol. 2002 Dec 1;169(11):6522-9
12444163
Immunity. 2006 Jan;24(1):93-103
16413926
J Leukoc Biol. 2010 Dec;88(6):1081-7
20699362
Cell Metab. 2005 Mar;1(3):201-13
16054063
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10809-13
7971966
J Clin Invest. 2006 Mar;116(3):607-14
16511593
J Immunol. 2004 Dec 15;173(12):7416-25
15585867
Nat Rev Microbiol. 2009 Feb;7(2):99-109
19148178
Science. 2010 Jun 25;328(5986):1703-5
20508090
Cell Metab. 2007 Jan;5(1):73-9
17189208
J Exp Med. 2004 Aug 16;200(4):437-45
15302901
J Biol Chem. 2006 Feb 24;281(8):4920-30
16354658
Mol Cell Biol. 2003 Aug;23(16):5780-9
12897148
Genes Dev. 1995 May 1;9(9):1033-45
7744246
J Biol Chem. 2005 Oct 21;280(42):35391-8
16030018
Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17813-8
15601766
J Immunol. 2009 Feb 1;182(3):1648-59
19155514
J Biol Chem. 1974 Nov 25;249(22):7306-14
4436312
J Exp Med. 2004 Aug 16;200(4):535-40
15302900
J Immunol. 2008 Mar 15;180(6):4116-23
18322222
J Biol Chem. 1974 Oct 10;249(19):6057-61
4472550
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10588-93
9380679
Gene Ther. 2004 Apr;11(8):675-82
14724673
J Clin Immunol. 2010 Sep;30(5):693-702
20490635
J Biol Chem. 1998 Dec 18;273(51):34316-27
9852097
J Exp Med. 1999 Jan 18;189(2):413-22
9892623
Nat Med. 2003 Feb;9(2):213-9
12524534
Mol Cell. 2001 Jan;7(1):161-71
11172721
Cell. 2004 Oct 15;119(2):299-309
15479645
Microbes Infect. 2008 Jul;10(9):1041-50
18775788
Mol Endocrinol. 2003 Jun;17(6):1019-26
12663743
J Immunol. 2004 Nov 1;173(9):5652-8
15494516
Cell Microbiol. 2008 Jan;10(1):41-52
17662073