Home LiteratureArticle Details
PMID: 16304607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases.

PLoS pathogens ·Vol. 1 ·No. 3 ·2005-11-00 ·Pages e24

Martens S, Parvanova I, Zerrahn J, Griffiths G, Schell G, Reichmann G, Howard JC

Abstract

The p47 GTPases are essential for interferon-gamma-induced cell-autonomous immunity against the protozoan parasite, Toxoplasma gondii, in mice, but the mechanism of resistance is poorly understood. We show that the p47 GTPases, including IIGP1, accumulate at vacuoles containing T. gondii. The accumulation is GTP-dependent and requires live parasites. Vacuolar IIGP1 accumulations undergo a maturation-like process accompanied by vesiculation of the parasitophorous vacuole membrane. This culminates in disruption of the parasitophorous vacuole and finally of the parasite itself. Over-expression of IIGP1 leads to accelerated vacuolar disruption whereas a dominant negative form of IIGP1 interferes with interferon-gamma-mediated killing of intracellular parasites. Targeted deletion of the IIGP1 gene results in partial loss of the IFN-gamma-mediated T. gondii growth restriction in mouse astrocytes.

MeSH Terms
Animals Animals, Newborn Astrocytes/parasitology Cells, Cultured GTP Phosphohydrolases/physiology Host-Parasite Interactions Humans Immunity, Innate Male Mice Mice, Inbred C57BL Toxoplasma/metabolism Vacuoles/metabolism,parasitology
Chemicals
GTP Phosphohydrolases Iigp1 protein, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Martens Sascha
Institute for Genetics, University of Cologne, Cologne, Germany.
Parvanova Iana
Zerrahn Jens
Griffiths Gareth
Schell Gudrun
Reichmann Gaby
Howard Jonathan C
References (60)
60 references, click to expand
  1. Invasion by Toxoplasma gondii establishes a moving junction that selectively excludes host cell plasma membrane proteins on the basis of their membrane anchoring.
    J Exp Med. 1999 Dec 20;190(12):1783-92 PMID: 10601353
  2. Toxoplasma gondii: fusion competence of parasitophorous vacuoles in Fc receptor-transfected fibroblasts.
    Science. 1990 Aug 10;249(4969):641-6 PMID: 2200126
  3. Investigation into the mechanism of gamma interferon-mediated inhibition of Toxoplasma gondii in murine astrocytes.
    Infect Immun. 2000 Jun;68(6):3426-30 PMID: 10816494
  4. The Toxoplasma gondii protein ROP2 mediates host organelle association with the parasitophorous vacuole membrane.
    J Cell Biol. 2001 Jul 9;154(1):95-108 PMID: 11448993
  5. Inactivation of LRG-47 and IRG-47 reveals a family of interferon gamma-inducible genes with essential, pathogen-specific roles in resistance to infection.
    J Exp Med. 2001 Jul 16;194(2):181-8 PMID: 11457893
  6. Gamma interferon-induced inhibition of Toxoplasma gondii in astrocytes is mediated by IGTP.
    Infect Immun. 2001 Sep;69(9):5573-6 PMID: 11500431
  7. Microinjection and growth of bacteria in the cytosol of mammalian host cells.
    Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12221-6 PMID: 11572936
  8. Phagocytosis of microbes: complexity in action.
    Annu Rev Immunol. 2002;20:825-52 PMID: 11861619
  9. The IFN-inducible Golgi- and endoplasmic reticulum- associated 47-kDa GTPase IIGP is transiently expressed during listeriosis.
    J Immunol. 2002 Apr 1;168(7):3428-36 PMID: 11907101
  10. Growth and killing of a Salmonella enterica serovar Typhimurium sifA mutant strain in the cytosol of different host cell lines.
    Microbiology. 2002 Sep;148(Pt 9):2705-15 PMID: 12213917
  11. The function of gamma interferon-inducible GTP-binding protein IGTP in host resistance to Toxoplasma gondii is Stat1 dependent and requires expression in both hematopoietic and nonhematopoietic cellular compartments.
    Infect Immun. 2002 Dec;70(12):6933-9 PMID: 12438372
  12. IIGP1, an interferon-gamma-inducible 47-kDa GTPase of the mouse, showing cooperative enzymatic activity and GTP-dependent multimerization.
    J Biol Chem. 2003 Aug 1;278(31):29336-43 PMID: 12732635
  13. Cultured astrocytes express toll-like receptors for bacterial products.
    Glia. 2003 Sep;43(3):281-91 PMID: 12898707
  14. Immune control of tuberculosis by IFN-gamma-inducible LRG-47.
    Science. 2003 Oct 24;302(5645):654-9 PMID: 14576437
  15. Mice deficient in LRG-47 display increased susceptibility to mycobacterial infection associated with the induction of lymphopenia.
    J Immunol. 2004 Jan 15;172(2):1163-8 PMID: 14707092
  16. The dynamin superfamily: universal membrane tubulation and fission molecules?
    Nat Rev Mol Cell Biol. 2004 Feb;5(2):133-47 PMID: 15040446
  17. p47 GTPases: regulators of immunity to intracellular pathogens.
    Nat Rev Immunol. 2004 Feb;4(2):100-9 PMID: 15040583
  18. Intracellular parasite invasion strategies.
    Science. 2004 Apr 9;304(5668):248-53 PMID: 15073368
  19. IIGP, a member of the IFN inducible and microbial defense mediating 47 kDa GTPase family, interacts with the microtubule binding protein hook3.
    J Cell Sci. 2004 Apr 1;117(Pt 9):1747-56 PMID: 15075236
  20. Toxoplasma gondii triggers myeloid differentiation factor 88-dependent IL-12 and chemokine ligand 2 (monocyte chemoattractant protein 1) responses using distinct parasite molecules and host receptors.
    J Immunol. 2004 Jun 1;172(11):6954-60 PMID: 15153515
  21. Mechanisms regulating the positioning of mouse p47 resistance GTPases LRG-47 and IIGP1 on cellular membranes: retargeting to plasma membrane induced by phagocytosis.
    J Immunol. 2004 Aug 15;173(4):2594-606 PMID: 15294976
  22. Crystal structure of IIGP1: a paradigm for interferon-inducible p47 resistance GTPases.
    Mol Cell. 2004 Sep 10;15(5):727-39 PMID: 15350217
  23. The IRG-47 gene is IFN-gamma induced in B cells and encodes a protein with GTP-binding motifs.
    J Immunol. 1992 May 15;148(10):3275-81 PMID: 1578148
  24. Targeted disruption of the MHC class II Aa gene in C57BL/6 mice.
    Int Immunol. 1993 Aug;5(8):957-64 PMID: 8398989
  25. Kinetics and pattern of organelle exocytosis during Toxoplasma gondii/host-cell interaction.
    Parasitol Res. 1993;79(5):402-8 PMID: 8415546
  26. The parasitophorous vacuole membrane surrounding intracellular Toxoplasma gondii functions as a molecular sieve.
    Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):509-13 PMID: 8290555
  27. Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii.
    J Immunol. 1994 Sep 15;153(6):2533-43 PMID: 7915739
  28. Isolation of a gene encoding a developmentally regulated T cell-specific protein with a guanine nucleotide triphosphate-binding motif.
    J Immunol. 1995 Feb 15;154(4):1724-34 PMID: 7836757
  29. Development of antimalaria immunity in mice lacking IFN-gamma receptor.
    J Immunol. 1995 May 15;154(10):5338-44 PMID: 7537305
  30. Regulated secretion of multi-lamellar vesicles leads to formation of a tubulo-vesicular network in host-cell vacuoles occupied by Toxoplasma gondii.
    J Cell Sci. 1995 Apr;108 ( Pt 4):1669-77 PMID: 7615684
  31. Invasion of Toxoplasma gondii occurs by active penetration of the host cell.
    J Cell Sci. 1995 Jun;108 ( Pt 6):2457-64 PMID: 7673360
  32. Identification of an endotoxin and IFN-inducible cDNA: possible identification of a novel protein family.
    J Leukoc Biol. 1995 Oct;58(4):477-84 PMID: 7561525
  33. A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells.
    Nucleic Acids Res. 1995 Dec 25;23(24):5080-1 PMID: 8559668
  34. Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite.
    Cell. 1996 Mar 22;84(6):933-9 PMID: 8601316
  35. Toxoplasma invasion: the parasitophorous vacuole is formed from host cell plasma membrane and pinches off via a fission pore.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8413-8 PMID: 8710885
  36. Identification of a novel GTPase, the inducibly expressed GTPase, that accumulates in response to interferon gamma.
    J Biol Chem. 1996 Aug 23;271(34):20399-405 PMID: 8702776
  37. In the absence of endogenous IFN-gamma, mice develop unimpaired IL-12 responses to Toxoplasma gondii while failing to control acute infection.
    J Immunol. 1996 Nov 1;157(9):4045-54 PMID: 8892638
  38. The inducibly expressed GTPase localizes to the endoplasmic reticulum, independently of GTP binding.
    J Biol Chem. 1997 Apr 18;272(16):10639-45 PMID: 9099712
  39. Cytokine responses induced by Toxoplasma gondii in astrocytes and microglial cells.
    Eur J Immunol. 1997 Jun;27(6):1539-48 PMID: 9209508
  40. Perforin-mediated cytolysis plays a limited role in host resistance to Toxoplasma gondii.
    J Immunol. 1997 Aug 15;159(4):1903-8 PMID: 9257855
  41. Association of host cell endoplasmic reticulum and mitochondria with the Toxoplasma gondii parasitophorous vacuole membrane: a high affinity interaction.
    J Cell Sci. 1997 Sep;110 ( Pt 17):2117-28 PMID: 9378762
  42. Infection of mice lacking the common cytokine receptor gamma-chain (gamma(c)) reveals an unexpected role for CD4+ T lymphocytes in early IFN-gamma-dependent resistance to Toxoplasma gondii.
    J Immunol. 1998 Mar 15;160(6):2565-9 PMID: 9510152
  43. GRA7, an excretory 29 kDa Toxoplasma gondii dense granule antigen released by infected host cells.
    Mol Biochem Parasitol. 1998 Mar 15;91(2):251-62 PMID: 9566518
  44. The parasitophorous vacuole membrane surrounding Plasmodium and Toxoplasma: an unusual compartment in infected cells.
    J Cell Sci. 1998 Jun;111 ( Pt 11):1467-75 PMID: 9580555
  45. The amphipathic alpha helices of the toxoplasma protein GRA2 mediate post-secretory membrane association.
    J Cell Sci. 1998 Aug;111 ( Pt 15):2171-80 PMID: 9664038
  46. Effect of cytokines on growth of Toxoplasma gondii in murine astrocytes.
    Infect Immun. 1998 Oct;66(10):4989-93 PMID: 9746608
  47. Quantitative immunolocalization of a P29 protein (GRA7), a new antigen of toxoplasma gondii.
    J Histochem Cytochem. 1998 Dec;46(12):1411-22 PMID: 9815283
  48. Two families of GTPases dominate the complex cellular response to IFN-gamma.
    J Immunol. 1998 Dec 15;161(12):6715-23 PMID: 9862701
  49. Effector cells of both nonhemopoietic and hemopoietic origin are required for interferon (IFN)-gamma- and tumor necrosis factor (TNF)-alpha-dependent host resistance to the intracellular pathogen, Toxoplasma gondii.
    J Exp Med. 1999 Apr 5;189(7):1083-92 PMID: 10190899
  50. Toxoplasma gondii resides in a vacuole that avoids fusion with host cell endocytic and exocytic vesicular trafficking pathways.
    Exp Parasitol. 1999 Jun;92(2):87-99 PMID: 10366534
  51. Class I major histocompatibility complex presentation of antigens that escape from the parasitophorous vacuole of Toxoplasma gondii.
    Infect Immun. 2005 Feb;73(2):703-11 PMID: 15664908
  52. Eating oneself and uninvited guests: autophagy-related pathways in cellular defense.
    Cell. 2005 Jan 28;120(2):159-62 PMID: 15680321
  53. p47 GTPases regulate Toxoplasma gondii survival in activated macrophages.
    Infect Immun. 2005 Jun;73(6):3278-86 PMID: 15908352
  54. Chlamydial IFN-gamma immune evasion is linked to host infection tropism.
    Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10658-63 PMID: 16020528
  55. Proteomic analysis of rhoptry organelles reveals many novel constituents for host-parasite interactions in Toxoplasma gondii.
    J Biol Chem. 2005 Oct 7;280(40):34245-58 PMID: 16002398
  56. The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage.
    Genome Biol. 2005;6(11):R92 PMID: 16277747
  57. Molecular partitioning during host cell penetration by Toxoplasma gondii.
    Traffic. 2004 Nov;5(11):855-67 PMID: 15479451
  58. Specific labeling of intracellular Toxoplasma gondii with uracil.
    J Protozool. 1977 Aug;24(3):449-53 PMID: 21288
  59. Characterization of a family of rhoptry proteins of Toxoplasma gondii.
    Mol Biochem Parasitol. 1988 Jun;29(2-3):203-11 PMID: 3045541
  60. Pathogen-specific loss of host resistance in mice lacking the IFN-gamma-inducible gene IGTP.
    Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):751-5 PMID: 10639151
Article Info
Journal
PLoS pathogens
Abbr.
PLoS Pathog
ISSN
1553-7366
DOI
10.1371/journal.ppat.0010024
Published
2005-11-00
Epub
2005-00-18
Pages
e24
Language
English
Region
United States
NLM ID
101238921
PMCID
PMC1287907
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.ppat.0010024 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