Murine Guanylate Binding Protein 2 (mGBP2) controls Toxoplasma gondii replication
IFN-γ orchestrates the host response against intracellular pathogens. Members of the guanylate binding proteins (GBP) comprise the most abundant IFN-γ-induced transcriptional response. mGBPs are GTPases that are specifically up-regulated by IFN-γ, other proinflammatory cytokines, toll-like receptor...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2013-01, Vol.110 (1), p.294-299 |
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| creator | Degrandi, Daniel Kravets, Elisabeth Konermann, Carolin Beuter-Gunia, Cornelia Klümpers, Verena Lahme, Sarah Wischmann, Eva Mausberg, Anne K. Beer-Hammer, Sandra Pfeffer, Klaus |
| description | IFN-γ orchestrates the host response against intracellular pathogens. Members of the guanylate binding proteins (GBP) comprise the most abundant IFN-γ-induced transcriptional response. mGBPs are GTPases that are specifically up-regulated by IFN-γ, other proinflammatory cytokines, toll-like receptor agonists, as well as in response to Listeria monocytogenes and Toxoplasma gondii infection. mGBP2 localizes at the parasitophorous vacuole (PV) of T. gondii; however, the molecular function of mGBP2 and its domains in T. gondii infection is not known. Here, we show that mGBP2 is highly expressed in several cell types, including T and B cells after stimulation. We provide evidence that the Cterminal domain is sufficient and essential for recruitment to the T. gondii PV. Functionally, mGBP2 reduces T. gondii proliferation because mGBP2-deficient cells display defects in the replication control of T. gondii. Ultimately, mGBP2-deficient mice reveal a marked immune susceptibility to T. gondii. Taken together, mGBP2 is an essential immune effector molecule mediating antiparasitic resistance. |
| doi_str_mv | 10.1073/pnas.1205635110 |
| format | Article |
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Members of the guanylate binding proteins (GBP) comprise the most abundant IFN-γ-induced transcriptional response. mGBPs are GTPases that are specifically up-regulated by IFN-γ, other proinflammatory cytokines, toll-like receptor agonists, as well as in response to Listeria monocytogenes and Toxoplasma gondii infection. mGBP2 localizes at the parasitophorous vacuole (PV) of T. gondii; however, the molecular function of mGBP2 and its domains in T. gondii infection is not known. Here, we show that mGBP2 is highly expressed in several cell types, including T and B cells after stimulation. We provide evidence that the Cterminal domain is sufficient and essential for recruitment to the T. gondii PV. Functionally, mGBP2 reduces T. gondii proliferation because mGBP2-deficient cells display defects in the replication control of T. gondii. Ultimately, mGBP2-deficient mice reveal a marked immune susceptibility to T. gondii. Taken together, mGBP2 is an essential immune effector molecule mediating antiparasitic resistance.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1205635110</identifier><identifier>PMID: 23248289</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>agonists ; Animals ; antiparasitic agents ; Astrocytes ; Binding sites ; Biological Sciences ; Blotting, Western ; Cysts ; cytokines ; Fluorescent Antibody Technique ; Gene expression ; GTP-Binding Proteins - genetics ; GTP-Binding Proteins - metabolism ; guanosinetriphosphatase ; Host-Pathogen Interactions ; Immunity ; Infections ; Interferon ; interferon-gamma ; Interferon-gamma - immunology ; Interferons ; Listeria monocytogenes ; Lymphocytes - immunology ; Lymphocytes - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Confocal ; NIH 3T3 Cells ; Parasites ; Parasitic protozoa ; Parasitism ; Pathogens ; Proteins ; Reproduction - physiology ; Rodents ; Toll-like receptors ; Toxoplasma - physiology ; Toxoplasma gondii ; Toxoplasmosis, Animal - immunology ; transcription (genetics) ; Vacuoles</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2013-01, Vol.110 (1), p.294-299</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jan 2, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-1660e4db06bdb838724bbf9d104140ce51fd154eb9fb9f9d646c08f86434a36e3</citedby><cites>FETCH-LOGICAL-c457t-1660e4db06bdb838724bbf9d104140ce51fd154eb9fb9f9d646c08f86434a36e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/1.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/42553934$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/42553934$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27905,27906,53772,53774,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23248289$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Degrandi, Daniel</creatorcontrib><creatorcontrib>Kravets, Elisabeth</creatorcontrib><creatorcontrib>Konermann, Carolin</creatorcontrib><creatorcontrib>Beuter-Gunia, Cornelia</creatorcontrib><creatorcontrib>Klümpers, Verena</creatorcontrib><creatorcontrib>Lahme, Sarah</creatorcontrib><creatorcontrib>Wischmann, Eva</creatorcontrib><creatorcontrib>Mausberg, Anne K.</creatorcontrib><creatorcontrib>Beer-Hammer, Sandra</creatorcontrib><creatorcontrib>Pfeffer, Klaus</creatorcontrib><title>Murine Guanylate Binding Protein 2 (mGBP2) controls Toxoplasma gondii replication</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>IFN-γ orchestrates the host response against intracellular pathogens. Members of the guanylate binding proteins (GBP) comprise the most abundant IFN-γ-induced transcriptional response. mGBPs are GTPases that are specifically up-regulated by IFN-γ, other proinflammatory cytokines, toll-like receptor agonists, as well as in response to Listeria monocytogenes and Toxoplasma gondii infection. mGBP2 localizes at the parasitophorous vacuole (PV) of T. gondii; however, the molecular function of mGBP2 and its domains in T. gondii infection is not known. Here, we show that mGBP2 is highly expressed in several cell types, including T and B cells after stimulation. We provide evidence that the Cterminal domain is sufficient and essential for recruitment to the T. gondii PV. Functionally, mGBP2 reduces T. gondii proliferation because mGBP2-deficient cells display defects in the replication control of T. gondii. Ultimately, mGBP2-deficient mice reveal a marked immune susceptibility to T. gondii. Taken together, mGBP2 is an essential immune effector molecule mediating antiparasitic resistance.</description><subject>agonists</subject><subject>Animals</subject><subject>antiparasitic agents</subject><subject>Astrocytes</subject><subject>Binding sites</subject><subject>Biological Sciences</subject><subject>Blotting, Western</subject><subject>Cysts</subject><subject>cytokines</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene expression</subject><subject>GTP-Binding Proteins - genetics</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>guanosinetriphosphatase</subject><subject>Host-Pathogen Interactions</subject><subject>Immunity</subject><subject>Infections</subject><subject>Interferon</subject><subject>interferon-gamma</subject><subject>Interferon-gamma - immunology</subject><subject>Interferons</subject><subject>Listeria monocytogenes</subject><subject>Lymphocytes - immunology</subject><subject>Lymphocytes - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Microscopy, Confocal</subject><subject>NIH 3T3 Cells</subject><subject>Parasites</subject><subject>Parasitic protozoa</subject><subject>Parasitism</subject><subject>Pathogens</subject><subject>Proteins</subject><subject>Reproduction - physiology</subject><subject>Rodents</subject><subject>Toll-like receptors</subject><subject>Toxoplasma - physiology</subject><subject>Toxoplasma gondii</subject><subject>Toxoplasmosis, Animal - immunology</subject><subject>transcription (genetics)</subject><subject>Vacuoles</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9rFDEYhoModq2ePSkBL_Uw7Zefk1wEW3QVKlao55CZyaxZZpIxmSntf2-Wrlv1IgRy-J7v4U1ehF4SOCVQs7Mp2HxKKAjJBCHwCK0IaFJJruExWgHQulKc8iP0LOctAGih4Ck6ooxyRZVeoW9fluSDw-vFhrvBzg6f-9D5sMFXKc7OB0zxybg-v6JvcRvDnOKQ8XW8jdNg82jxJhba4-Smwbd29jE8R096O2T3Yn8fo-8fP1xffKouv64_X7y_rFou6rkiUoLjXQOy6RrFVE150_S6I8AJh9YJ0ndEcNfovhzdSS5bUL2SnHHLpGPH6N29d1qa0XWtK-HsYKbkR5vuTLTe_D0J_ofZxBvDBFOU0iI42QtS_Lm4PJvR59YNgw0uLtkQBYwQrSj_P0prRiSVqi7om3_QbVxSKD9RKFnSU6ZYoc7uqTbFnJPrD7kJmF2zZteseWi2bLz-87kH_neVBXi1B3abB93OZ6jmD_NtnmM6AJwKwTTj7BeO4LGn</recordid><startdate>20130102</startdate><enddate>20130102</enddate><creator>Degrandi, Daniel</creator><creator>Kravets, Elisabeth</creator><creator>Konermann, Carolin</creator><creator>Beuter-Gunia, Cornelia</creator><creator>Klümpers, Verena</creator><creator>Lahme, Sarah</creator><creator>Wischmann, Eva</creator><creator>Mausberg, Anne K.</creator><creator>Beer-Hammer, Sandra</creator><creator>Pfeffer, Klaus</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20130102</creationdate><title>Murine Guanylate Binding Protein 2 (mGBP2) controls Toxoplasma gondii replication</title><author>Degrandi, Daniel ; 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Members of the guanylate binding proteins (GBP) comprise the most abundant IFN-γ-induced transcriptional response. mGBPs are GTPases that are specifically up-regulated by IFN-γ, other proinflammatory cytokines, toll-like receptor agonists, as well as in response to Listeria monocytogenes and Toxoplasma gondii infection. mGBP2 localizes at the parasitophorous vacuole (PV) of T. gondii; however, the molecular function of mGBP2 and its domains in T. gondii infection is not known. Here, we show that mGBP2 is highly expressed in several cell types, including T and B cells after stimulation. We provide evidence that the Cterminal domain is sufficient and essential for recruitment to the T. gondii PV. Functionally, mGBP2 reduces T. gondii proliferation because mGBP2-deficient cells display defects in the replication control of T. gondii. Ultimately, mGBP2-deficient mice reveal a marked immune susceptibility to T. gondii. Taken together, mGBP2 is an essential immune effector molecule mediating antiparasitic resistance.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>23248289</pmid><doi>10.1073/pnas.1205635110</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | agonists Animals antiparasitic agents Astrocytes Binding sites Biological Sciences Blotting, Western Cysts cytokines Fluorescent Antibody Technique Gene expression GTP-Binding Proteins - genetics GTP-Binding Proteins - metabolism guanosinetriphosphatase Host-Pathogen Interactions Immunity Infections Interferon interferon-gamma Interferon-gamma - immunology Interferons Listeria monocytogenes Lymphocytes - immunology Lymphocytes - metabolism Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Confocal NIH 3T3 Cells Parasites Parasitic protozoa Parasitism Pathogens Proteins Reproduction - physiology Rodents Toll-like receptors Toxoplasma - physiology Toxoplasma gondii Toxoplasmosis, Animal - immunology transcription (genetics) Vacuoles |
| title | Murine Guanylate Binding Protein 2 (mGBP2) controls Toxoplasma gondii replication |
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