Toxoplasma Polymorphic Effectors Determine Macrophage Polarization and Intestinal Inflammation
European and North American strains of the parasite Toxoplasma gondii belong to three distinct clonal lineages, type I, type II, and type III, which differ in virulence. Understanding the basis of Toxoplasma strain differences and how secreted effectors work to achieve chronic infection is a major g...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/92554 |
| _version_ | 1826191621866127360 |
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| author | Jensen, Kirk D. C. Wang, Yiding Wojno, Elia D. Tait Shastri, Anjali J. Hu, Kenneth Cornel, Lara Boedec, Erwan Ong, Yi-Ching Chien, Yueh-hsiu Hunter, Christopher A. Boothroyd, John C. Saeij, Jeroen |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Jensen, Kirk D. C. Wang, Yiding Wojno, Elia D. Tait Shastri, Anjali J. Hu, Kenneth Cornel, Lara Boedec, Erwan Ong, Yi-Ching Chien, Yueh-hsiu Hunter, Christopher A. Boothroyd, John C. Saeij, Jeroen |
| author_sort | Jensen, Kirk D. C. |
| collection | MIT |
| description | European and North American strains of the parasite Toxoplasma gondii belong to three distinct clonal lineages, type I, type II, and type III, which differ in virulence. Understanding the basis of Toxoplasma strain differences and how secreted effectors work to achieve chronic infection is a major goal of current research. Here we show that type I and III infected macrophages, a cell type required for host immunity to Toxoplasma, are alternatively activated, while type II infected macrophages are classically activated. The Toxoplasma rhoptry kinase ROP16, which activates STAT6, is responsible for alternative activation. The Toxoplasma dense granule protein GRA15, which activates NF-κB, promotes classical activation by type II parasites. These effectors antagonistically regulate many of the same genes, and mice infected with type II parasites expressing type I ROP16 are protected against Toxoplasma-induced ileitis. Thus, polymorphisms in determinants that modulate macrophage activation influence the ability of Toxoplasma to establish a chronic infection. |
| first_indexed | 2024-09-23T08:59:06Z |
| format | Article |
| id | mit-1721.1/92554 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:59:06Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/925542022-09-30T12:35:05Z Toxoplasma Polymorphic Effectors Determine Macrophage Polarization and Intestinal Inflammation Jensen, Kirk D. C. Wang, Yiding Wojno, Elia D. Tait Shastri, Anjali J. Hu, Kenneth Cornel, Lara Boedec, Erwan Ong, Yi-Ching Chien, Yueh-hsiu Hunter, Christopher A. Boothroyd, John C. Saeij, Jeroen Massachusetts Institute of Technology. Department of Biology Jensen, Kirk D. C. Wang, Yiding Hu, Kenneth Cornel, Lara Boedec, Erwan Saeij, Jeroen European and North American strains of the parasite Toxoplasma gondii belong to three distinct clonal lineages, type I, type II, and type III, which differ in virulence. Understanding the basis of Toxoplasma strain differences and how secreted effectors work to achieve chronic infection is a major goal of current research. Here we show that type I and III infected macrophages, a cell type required for host immunity to Toxoplasma, are alternatively activated, while type II infected macrophages are classically activated. The Toxoplasma rhoptry kinase ROP16, which activates STAT6, is responsible for alternative activation. The Toxoplasma dense granule protein GRA15, which activates NF-κB, promotes classical activation by type II parasites. These effectors antagonistically regulate many of the same genes, and mice infected with type II parasites expressing type I ROP16 are protected against Toxoplasma-induced ileitis. Thus, polymorphisms in determinants that modulate macrophage activation influence the ability of Toxoplasma to establish a chronic infection. Cancer Research Institute (New York, N.Y.) (Irvington Postdoctoral Fellowship) National Institutes of Health (U.S.) (AI42334) National Institutes of Health (U.S.) (AI21423) National Institutes of Health (U.S.) (AI73756) National Institutes of Health (U.S.) (AI33431) National Institutes of Health (U.S.) (U19 AI057229) National Institutes of Health (U.S.) (AI080621) 2014-12-30T18:47:49Z 2014-12-30T18:47:49Z 2011-06 2011-02 Article http://purl.org/eprint/type/JournalArticle 19313128 http://hdl.handle.net/1721.1/92554 Jensen, Kirk D.C., Yiding Wang, Elia D. Tait Wojno, Anjali J. Shastri, Kenneth Hu, Lara Cornel, Erwan Boedec, et al. “Toxoplasma Polymorphic Effectors Determine Macrophage Polarization and Intestinal Inflammation.” Cell Host & Microbe 9, no. 6 (June 2011): 472–483. © 2011 Elsevier Inc. en_US http://dx.doi.org/10.1016/j.chom.2011.04.015 Cell Host and Microbe Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Jensen, Kirk D. C. Wang, Yiding Wojno, Elia D. Tait Shastri, Anjali J. Hu, Kenneth Cornel, Lara Boedec, Erwan Ong, Yi-Ching Chien, Yueh-hsiu Hunter, Christopher A. Boothroyd, John C. Saeij, Jeroen Toxoplasma Polymorphic Effectors Determine Macrophage Polarization and Intestinal Inflammation |
| title | Toxoplasma Polymorphic Effectors Determine Macrophage Polarization and Intestinal Inflammation |
| title_full | Toxoplasma Polymorphic Effectors Determine Macrophage Polarization and Intestinal Inflammation |
| title_fullStr | Toxoplasma Polymorphic Effectors Determine Macrophage Polarization and Intestinal Inflammation |
| title_full_unstemmed | Toxoplasma Polymorphic Effectors Determine Macrophage Polarization and Intestinal Inflammation |
| title_short | Toxoplasma Polymorphic Effectors Determine Macrophage Polarization and Intestinal Inflammation |
| title_sort | toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation |
| url | http://hdl.handle.net/1721.1/92554 |
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