Home LiteratureArticle Details
PMID: 18769721 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

XIAP regulates cytosol-specific innate immunity to Listeria infection.

PLoS pathogens ·Vol. 4 ·No. 8 ·2008-08-29 ·Pages e1000142

Bauler LD, Duckett CS, O'Riordan MX

Abstract

The inhibitor of apoptosis protein (IAP) family has been implicated in immune regulation, but the mechanisms by which IAP proteins contribute to immunity are incompletely understood. We show here that X-linked IAP (XIAP) is required for innate immune control of Listeria monocytogenes infection. Mice deficient in XIAP had a higher bacterial burden 48 h after infection than wild-type littermates, and exhibited substantially decreased survival. XIAP enhanced NF-kappaB activation upon L. monocytogenes infection of activated macrophages, and prolonged phosphorylation of Jun N-terminal kinase (JNK) specifically in response to cytosolic bacteria. Additionally, XIAP promoted maximal production of pro-inflammatory cytokines upon bacterial infection in vitro or in vivo, or in response to combined treatment with NOD2 and TLR2 ligands. Together, our data suggest that XIAP regulates innate immune responses to L. monocytogenes infection by potentiating synergy between Toll-like receptors (TLRs) and Nod-like receptors (NLRs) through activation of JNK- and NF-kappaB-dependent signaling.

MeSH Terms
Animals Cells, Cultured Cytokines/genetics,immunology,metabolism Cytosol/immunology,metabolism Immunity, Innate/genetics JNK Mitogen-Activated Protein Kinases/genetics,immunology,metabolism Listeria monocytogenes/immunology,metabolism Listeriosis/genetics,immunology,metabolism Macrophages/immunology,metabolism,microbiology Mice Mice, Knockout NF-kappa B/genetics,immunology Nod2 Signaling Adaptor Protein/agonists,genetics,immunology,metabolism Signal Transduction/genetics,immunology Toll-Like Receptor 2/agonists,genetics,immunology,metabolism X-Linked Inhibitor of Apoptosis Protein/genetics,immunology,metabolism
Chemicals
Cytokines NF-kappa B Nod2 Signaling Adaptor Protein Nod2 protein, mouse Tlr2 protein, mouse Toll-Like Receptor 2 X-Linked Inhibitor of Apoptosis Protein JNK Mitogen-Activated Protein Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bauler Laura D
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Duckett Colin S
O'Riordan Mary X D
References (65)
65 references, click to expand
  1. The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands.
    Immunity. 2008 Feb;28(2):246-57 PMID: 18261938
  2. Innate recognition of bacteria by a macrophage cytosolic surveillance pathway.
    Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13861-6 PMID: 12359878
  3. Cooperation of Toll-like receptor signals in innate immune defence.
    Nat Rev Immunol. 2007 Mar;7(3):179-90 PMID: 17318230
  4. Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes.
    Nature. 1993 Aug 26;364(6440):798-802 PMID: 8395024
  5. Inhibitor of apoptosis protein cIAP2 is essential for lipopolysaccharide-induced macrophage survival.
    Mol Cell Biol. 2006 Jan;26(2):699-708 PMID: 16382159
  6. Selective activation of JNK1 is necessary for the anti-apoptotic activity of hILP.
    Proc Natl Acad Sci U S A. 1998 May 26;95(11):6015-20 PMID: 9600909
  7. Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity.
    PLoS Pathog. 2006 Mar;2(3):e18 PMID: 16552444
  8. A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors.
    EMBO J. 1996 Jun 3;15(11):2685-94 PMID: 8654366
  9. Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia.
    Infect Immun. 1995 Jun;63(6):2262-8 PMID: 7768607
  10. ILPIP, a novel anti-apoptotic protein that enhances XIAP-mediated activation of JNK1 and protection against apoptosis.
    J Biol Chem. 2002 Aug 23;277(34):30454-62 PMID: 12048196
  11. The Drosophila inhibitor of apoptosis protein DIAP2 functions in innate immunity and is essential to resist gram-negative bacterial infection.
    Mol Cell Biol. 2006 Nov;26(21):7821-31 PMID: 16894030
  12. The Drosophila inhibitor of apoptosis (IAP) DIAP2 is dispensable for cell survival, required for the innate immune response to gram-negative bacterial infection, and can be negatively regulated by the reaper/hid/grim family of IAP-binding apoptosis inducers.
    J Biol Chem. 2007 Jan 19;282(3):2056-68 PMID: 17068333
  13. Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection.
    J Exp Med. 2006 Apr 17;203(4):1093-104 PMID: 16606669
  14. Autophagy and inflammatory cell death, partners of innate immunity.
    Autophagy. 2005 Oct-Dec;1(3):174-6 PMID: 16874072
  15. Toll-like receptors.
    Annu Rev Immunol. 2003;21:335-76 PMID: 12524386
  16. XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway.
    EMBO J. 1999 Jan 4;18(1):179-87 PMID: 9878061
  17. Resistance to fever induction and impaired acute-phase response in interleukin-1 beta-deficient mice.
    Immunity. 1995 Jul;3(1):9-19 PMID: 7621081
  18. Toll-like receptors, RIG-I-like RNA helicases and the antiviral innate immune response.
    Immunol Cell Biol. 2007 Aug-Sep;85(6):435-45 PMID: 17667934
  19. An RNA interference screen identifies Inhibitor of Apoptosis Protein 2 as a regulator of innate immune signalling in Drosophila.
    EMBO Rep. 2005 Oct;6(10):979-84 PMID: 16170305
  20. Impaired immune and acute-phase responses in interleukin-6-deficient mice.
    Nature. 1994 Mar 24;368(6469):339-42 PMID: 8127368
  21. Listeriolysin O: a phagosome-specific lysin.
    Microbes Infect. 2007 Aug;9(10):1176-87 PMID: 17720603
  22. Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases.
    Microbiol Mol Biol Rev. 2006 Dec;70(4):1061-95 PMID: 17158707
  23. Synergistic stimulation of human monocytes and dendritic cells by Toll-like receptor 4 and NOD1- and NOD2-activating agonists.
    Eur J Immunol. 2005 Aug;35(8):2459-70 PMID: 16021602
  24. Innate immune recognition.
    Annu Rev Immunol. 2002;20:197-216 PMID: 11861602
  25. Synergistic enhancement of Toll-like receptor responses by NOD1 activation.
    Eur J Immunol. 2005 Aug;35(8):2471-6 PMID: 16021603
  26. Innate recognition of intracellular bacteria.
    Curr Opin Immunol. 2007 Feb;19(1):10-6 PMID: 17126540
  27. NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP.
    Nature. 1999 Oct 21;401(6755):818-22 PMID: 10548111
  28. Listeria monocytogenes activated p38 MAPK and induced IL-8 secretion in a nucleotide-binding oligomerization domain 1-dependent manner in endothelial cells.
    J Immunol. 2006 Jan 1;176(1):484-90 PMID: 16365441
  29. Uncoupling of the signaling and caspase-inhibitory properties of X-linked inhibitor of apoptosis.
    J Biol Chem. 2004 Mar 5;279(10):9023-9 PMID: 14701799
  30. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome.
    Nature. 2006 Nov 2;444(7115):110-4 PMID: 17080092
  31. Preexposure of murine macrophages to CpG oligonucleotide results in a biphasic tumor necrosis factor alpha response to subsequent lipopolysaccharide challenge.
    Infect Immun. 2001 Apr;69(4):2123-9 PMID: 11254566
  32. Regulation of Nod1-mediated signaling pathways.
    Cell Death Differ. 2007 Apr;14(4):830-9 PMID: 17186025
  33. XIAP: cell death regulation meets copper homeostasis.
    Arch Biochem Biophys. 2007 Jul 15;463(2):168-74 PMID: 17382285
  34. Activation of NF-kappa B by XIAP, the X chromosome-linked inhibitor of apoptosis, in endothelial cells involves TAK1.
    J Biol Chem. 2000 Jul 21;275(29):22064-8 PMID: 10807933
  35. The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens.
    Nat Immunol. 2007 Feb;8(2):198-205 PMID: 17187069
  36. Distinct roles of TLR2 and the adaptor ASC in IL-1beta/IL-18 secretion in response to Listeria monocytogenes.
    J Immunol. 2006 Apr 1;176(7):4337-42 PMID: 16547271
  37. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection.
    Cell. 1993 May 7;73(3):457-67 PMID: 8387893
  38. Mammalian NLR proteins; discriminating foe from friend.
    Immunol Cell Biol. 2007 Aug-Sep;85(6):495-502 PMID: 17680011
  39. Nucleotide-binding oligomerization domain-like receptors: intracellular pattern recognition molecules for pathogen detection and host defense.
    J Immunol. 2006 Sep 15;177(6):3507-13 PMID: 16951308
  40. Signal transduction pathways activated by the IL-1 receptor/toll-like receptor superfamily.
    Curr Top Microbiol Immunol. 2002;270:47-61 PMID: 12467243
  41. An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways.
    J Biol Chem. 2000 Sep 8;275(36):27823-31 PMID: 10880512
  42. IAP suppression of apoptosis involves distinct mechanisms: the TAK1/JNK1 signaling cascade and caspase inhibition.
    Mol Cell Biol. 2002 Mar;22(6):1754-66 PMID: 11865055
  43. Drosophila innate immunity: an evolutionary perspective.
    Nat Immunol. 2002 Feb;3(2):121-6 PMID: 11812988
  44. XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders.
    Mol Cell. 2006 Mar 17;21(6):775-85 PMID: 16543147
  45. Reciprocal cross-talk between Nod2 and TAK1 signaling pathways.
    J Biol Chem. 2004 Jun 11;279(24):25876-82 PMID: 15075345
  46. MyD88-dependent and MyD88-independent pathways in synergy, priming, and tolerance between TLR agonists.
    J Immunol. 2007 Jan 15;178(2):1164-71 PMID: 17202381
  47. Impaired macrophage listericidal and cytokine activities are responsible for the rapid death of Listeria monocytogenes-infected IFN-gamma receptor-deficient mice.
    J Immunol. 1997 Jun 1;158(11):5297-304 PMID: 9164949
  48. Immune responses to Listeria monocytogenes.
    Nat Rev Immunol. 2004 Oct;4(10):812-23 PMID: 15459672
  49. Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2.
    Science. 1999 Jul 30;285(5428):736-9 PMID: 10426996
  50. MyD88-dependent but Toll-like receptor 2-independent innate immunity to Listeria: no role for either in macrophage listericidal activity.
    J Immunol. 2002 Oct 1;169(7):3869-75 PMID: 12244184
  51. XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 dimerization.
    Mol Cell. 2007 Jun 8;26(5):689-702 PMID: 17560374
  52. Autophagy is an immediate macrophage response to Legionella pneumophila.
    Cell Microbiol. 2005 Jun;7(6):765-78 PMID: 15888080
  53. The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection.
    Nat Immunol. 2006 Mar;7(3):318-25 PMID: 16444259
  54. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract.
    Science. 2005 Feb 4;307(5710):731-4 PMID: 15692051
  55. X-linked IAP is a direct inhibitor of cell-death proteases.
    Nature. 1997 Jul 17;388(6639):300-4 PMID: 9230442
  56. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family.
    EMBO Rep. 2006 Oct;7(10):988-94 PMID: 17016456
  57. CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri.
    EMBO Rep. 2001 Aug;2(8):736-42 PMID: 11463746
  58. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis.
    Nature. 2001 Mar 1;410(6824):112-6 PMID: 11242052
  59. Characterization of early gamma interferon (IFN-gamma) expression during murine listeriosis: identification of NK1.1+ CD11c+ cells as the primary IFN-gamma-expressing cells.
    Infect Immun. 2007 Mar;75(3):1167-76 PMID: 17158904
  60. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines.
    J Exp Med. 1996 Jun 1;183(6):2593-603 PMID: 8676080
  61. Characterization of XIAP-deficient mice.
    Mol Cell Biol. 2001 May;21(10):3604-8 PMID: 11313486
  62. Regulation of the prfA transcriptional activator of Listeria monocytogenes: multiple promoter elements contribute to intracellular growth and cell-to-cell spread.
    Infect Immun. 1993 Jun;61(6):2537-44 PMID: 8388865
  63. IAP proteins: blocking the road to death's door.
    Nat Rev Mol Cell Biol. 2002 Jun;3(6):401-10 PMID: 12042762
  64. Mini-review: the role of peptidoglycan recognition in innate immunity.
    Eur J Immunol. 2004 Jul;34(7):1777-82 PMID: 15214025
  65. Inhibitor of apoptosis 2 and TAK1-binding protein are components of the Drosophila Imd pathway.
    EMBO J. 2005 Oct 5;24(19):3423-34 PMID: 16163390
Article Info
Journal
PLoS pathogens
Abbr.
PLoS Pathog
ISSN
1553-7374
DOI
10.1371/journal.ppat.1000142
Published
2008-08-29
Epub
2008-00-29
Pages
e1000142
Language
English
Region
United States
NLM ID
101238921
PMCID
PMC2516935
Subset
IM
Grants
NIGMS NIH HHS · R01 GM067827 · United States
External Links
PubMed source DOI: 10.1371/journal.ppat.1000142 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2