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          Institute: MPI für Infektionsbiologie     Collection: Department of Molecular Biology     Display Documents

ID: 572749.0, MPI für Infektionsbiologie / Department of Molecular Biology
The IFN-gamma-Inducible GTPase, Irga6, Protects Mice against Toxoplasma gondii but Not against Plasmodium berghei and Some Other Intracellular Pathogens
Authors:Liesenfeld, Oliver; Parvanova, Iana; Zerrahn, Jens; Han, Seong-Ji; Heinrich, Frederick; Munoz, Melba; Kaiser, Frank; Aebischer, Toni; Buch, Thorsten; Waisman, Ari; Reichmann, Gaby; Utermöhlen, Olaf; von Stebut, Esther; von Loewenich, Friederike; Bogdan, Christian; Specht, Sabine; Saeftel, Michael; Hoerauf, Achim; Mota, Maria M.; Könen-Waisman, Stephanie; Kaufmann, Stefan H. E.; Howard, Jonathan C.
Date of Publication (YYYY-MM-DD):2011-06-17
Title of Journal:PLoS ONE
Journal Abbrev.:PLoS One
Issue / Number:6
Sequence Number of Article:e20568
Copyright:© 2011 Liesenfeld et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Clearance of infection with intracellular pathogens in mice involves interferon-regulated GTPases of the IRG protein family. Experiments with mice genetically deficient in members of this family such as Irgm1(LRG-47), Irgm3(IGTP), and Irgd(IRG-47) has revealed a critical role in microbial clearance, especially for Toxoplasma gondii. The in vivo role of another member of this family, Irga6 (IIGP, IIGP1) has been studied in less detail. We investigated the susceptibility of two independently generated mouse strains deficient in Irga6 to in vivo infection with T. gondii, Mycobacterium tuberculosis, Leishmania mexicana, L. major, Listeria monocytogenes, Anaplasma phagocytophilum and Plasmodium berghei. Compared with wild-type mice, mice deficient in Irga6 showed increased susceptibility to oral and intraperitoneal infection with T. gondii but not to infection with the other organisms. Surprisingly, infection of Irga6-deficient mice with the related apicomplexan parasite, P. berghei, did not result in increased replication in the liver stage and no Irga6 (or any other IRG protein) was detected at the parasitophorous vacuole membrane in IFN-gamma-induced wild-type cells infected with P. berghei in vitro. Susceptibility to infection with T. gondii was associated with increased mortality and reduced time to death, increased numbers of inflammatory foci in the brains and elevated parasite loads in brains of infected Irga6-deficient mice. In vitro, Irga6-deficient macrophages and fibroblasts stimulated with IFN-gamma were defective in controlling parasite replication. Taken together, our results implicate Irga6 in the control of infection with T. gondii and further highlight the importance of the IRG system for resistance to this pathogen.
External Publication Status:published
Document Type:Article
Communicated by:Beate Löhr
Affiliations:MPI für Infektionsbiologie/Department of Immunology
MPI für Infektionsbiologie/Department of Molecular Biology
External Affiliations:[Liesenfeld, O; Han, SJ; Heinrich, F; Munoz, M] Charite Univ Med Berlin, Inst Microbiol & Hyg, Berlin, Germany; [Parvanova, I; Buch, T; Waisman, A; Konen-Waisman, S; Howard, JC] Univ Cologne, Inst Genet, D-5000 Cologne, Germany; [Reichmann, G] Univ Dusseldorf, Inst Med Microbiol, Dusseldorf, Germany; [Utermohlen, O] Univ Cologne, Inst Med Microbiol Immunol & Hyg, Cologne, Germany; [von Stebut, E] Johannes Gutenberg Univ Mainz, Dept Dermatol, Mainz, Germany; [von Loewenich, FD; Bogdan, C] Univ Hosp Freiburg, Dept Med Microbiol & Hyg, Inst Med Microbiol & Hyg, Freiburg, Germany; [Bogdan, C] Univ Hosp Erlangen, Microbiol Inst Clin Microbiol Immunol & Hyg, Erlangen, Germany; [Specht, S; Saeftel, M; Hoerauf, A] Univ Bonn, Inst Med Microbiol Immunol & Parasitol, D-5300 Bonn, Germany; [Mota, MM] Univ Lisbon, Malaria Unit, Inst Mol Med, Fac Med, P-1699 Lisbon, Portugal
Identifiers:ISI:000291737600010 [ID No:1]
ISSN:1932-6203 [ID No:2]
DOI:10.1371/journal.pone.0020568 [ID No:3]
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