Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It
IFN-γ is a major cytokine that mediates resistance against the intracellular parasite Toxoplasma gondii. The p65 guanylate-binding proteins (GBPs) are strongly induced by IFN-γ. We studied the behavior of murine GBP1 (mGBP1) upon infection with T. gondii in vitro and confirmed that IFN-γ-dependent r...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2012
|
| Online Access: | http://hdl.handle.net/1721.1/69115 https://orcid.org/0000-0002-1090-6071 |
| _version_ | 1826208710606716928 |
|---|---|
| author | Caradonna, Kacey Burleigh, Barbara A. Winter, Sebastian Virreira Niedelman, Wendy Leah Rosowski, Emily Elizabeth Julien, Lindsay Spooner, Eric Saeij, Jeroen Ploegh, Hidde Frickel, Eva-Maria Jensen, Kirk D. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Caradonna, Kacey Burleigh, Barbara A. Winter, Sebastian Virreira Niedelman, Wendy Leah Rosowski, Emily Elizabeth Julien, Lindsay Spooner, Eric Saeij, Jeroen Ploegh, Hidde Frickel, Eva-Maria Jensen, Kirk D. |
| author_sort | Caradonna, Kacey |
| collection | MIT |
| description | IFN-γ is a major cytokine that mediates resistance against the intracellular parasite Toxoplasma gondii. The p65 guanylate-binding proteins (GBPs) are strongly induced by IFN-γ. We studied the behavior of murine GBP1 (mGBP1) upon infection with T. gondii in vitro and confirmed that IFN-γ-dependent re-localization of mGBP1 to the parasitophorous vacuole (PV) correlates with the virulence type of the parasite. We identified three parasitic factors, ROP16, ROP18, and GRA15 that determine strain-specific accumulation of mGBP1 on the PV. These highly polymorphic proteins are held responsible for a large part of the strain-specific differences in virulence. Therefore, our data suggest that virulence of T. gondii in animals may rely in part on recognition by GBPs. However, phagosomes or vacuoles containing Trypanosoma cruzi did not recruit mGBP1. Co-immunoprecipitation revealed mGBP2, mGBP4, and mGBP5 as binding partners of mGBP1. Indeed, mGBP2 and mGBP5 co-localize with mGBP1 in T. gondii-infected cells. T. gondii thus elicits a cell-autonomous immune response in mice with GBPs involved. Three parasitic virulence factors and unknown IFN-γ-dependent host factors regulate this complex process. Depending on the virulence of the strains involved, numerous GBPs are brought to the PV as part of a large, multimeric structure to combat T. gondii. |
| first_indexed | 2024-09-23T14:10:35Z |
| format | Article |
| id | mit-1721.1/69115 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:10:35Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/691152022-09-28T19:01:14Z Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It Caradonna, Kacey Burleigh, Barbara A. Winter, Sebastian Virreira Niedelman, Wendy Leah Rosowski, Emily Elizabeth Julien, Lindsay Spooner, Eric Saeij, Jeroen Ploegh, Hidde Frickel, Eva-Maria Jensen, Kirk D. Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Ploegh, Hidde Winter, Sebastian Virreira Niedelman, Wendy Leah Jensen, Kirk D. C. Rosowski, Emily Elizabeth Julien, Lindsay Spooner, Eric Saeij, Jeroen Ploegh, Hidde Frickel, Eva-Maria IFN-γ is a major cytokine that mediates resistance against the intracellular parasite Toxoplasma gondii. The p65 guanylate-binding proteins (GBPs) are strongly induced by IFN-γ. We studied the behavior of murine GBP1 (mGBP1) upon infection with T. gondii in vitro and confirmed that IFN-γ-dependent re-localization of mGBP1 to the parasitophorous vacuole (PV) correlates with the virulence type of the parasite. We identified three parasitic factors, ROP16, ROP18, and GRA15 that determine strain-specific accumulation of mGBP1 on the PV. These highly polymorphic proteins are held responsible for a large part of the strain-specific differences in virulence. Therefore, our data suggest that virulence of T. gondii in animals may rely in part on recognition by GBPs. However, phagosomes or vacuoles containing Trypanosoma cruzi did not recruit mGBP1. Co-immunoprecipitation revealed mGBP2, mGBP4, and mGBP5 as binding partners of mGBP1. Indeed, mGBP2 and mGBP5 co-localize with mGBP1 in T. gondii-infected cells. T. gondii thus elicits a cell-autonomous immune response in mice with GBPs involved. Three parasitic virulence factors and unknown IFN-γ-dependent host factors regulate this complex process. Depending on the virulence of the strains involved, numerous GBPs are brought to the PV as part of a large, multimeric structure to combat T. gondii. National Institutes of Health (U.S.) Massachusetts Life Sciences Center (New Investigator Award) National Institute of General Medical Sciences (U.S.) (Pre-Doctoral Grant in the Biological Sciences (5-T32-GM007287-33)) Studienstiftung des deutschen Volkes Cancer Research Institute (New York, N.Y.) Cleo and Paul Schimmel Foundation Bayer Healthcare Human Frontier Science Program (Strasbourg, France) 2012-02-15T18:51:21Z 2012-02-15T18:51:21Z 2011-09 2011-05 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/69115 Virreira Winter, Sebastian et al. “Determinants of GBP Recruitment to Toxoplasma Gondii Vacuoles and the Parasitic Factors That Control It.” Ed. Silvia N. Moreno. PLoS ONE 6.9 (2011): e24434. Web. 15 Feb. 2012. https://orcid.org/0000-0002-1090-6071 en_US http://dx.doi.org/10.1371/journal.pone.0024434 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Caradonna, Kacey Burleigh, Barbara A. Winter, Sebastian Virreira Niedelman, Wendy Leah Rosowski, Emily Elizabeth Julien, Lindsay Spooner, Eric Saeij, Jeroen Ploegh, Hidde Frickel, Eva-Maria Jensen, Kirk D. Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It |
| title | Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It |
| title_full | Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It |
| title_fullStr | Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It |
| title_full_unstemmed | Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It |
| title_short | Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It |
| title_sort | determinants of gbp recruitment to toxoplasma gondii vacuoles and the parasitic factors that control it |
| url | http://hdl.handle.net/1721.1/69115 https://orcid.org/0000-0002-1090-6071 |
| work_keys_str_mv | AT caradonnakacey determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit AT burleighbarbaraa determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit AT wintersebastianvirreira determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit AT niedelmanwendyleah determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit AT rosowskiemilyelizabeth determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit AT julienlindsay determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit AT spoonereric determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit AT saeijjeroen determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit AT ploeghhidde determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit AT frickelevamaria determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit AT jensenkirkd determinantsofgbprecruitmenttotoxoplasmagondiivacuolesandtheparasiticfactorsthatcontrolit |