Toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through SNAT2 and CXCR4 pathways
The obligate intracellular parasite, Toxoplasma gondii, disseminates through its host inside infected immune cells. We hypothesize that parasite nutrient requirements lead to manipulation of migratory properties of the immune cell. We demonstrate that 1) T. gondii relies on glutamine for optimal inf...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2014
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| Online Access: | https://hdl.handle.net/10356/101134 http://hdl.handle.net/10220/24140 |
| _version_ | 1811680048104603648 |
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| author | De Miguel, Zurine Manley, Nathan C. Lee, I-Ping Evans, Andrew K. Yang, Cissy Works, Melissa G. Kumar, Vineet Sapolsky, Robert M. |
| author2 | Bogyo, Matthew |
| author_facet | Bogyo, Matthew De Miguel, Zurine Manley, Nathan C. Lee, I-Ping Evans, Andrew K. Yang, Cissy Works, Melissa G. Kumar, Vineet Sapolsky, Robert M. |
| author_sort | De Miguel, Zurine |
| collection | NTU |
| description | The obligate intracellular parasite, Toxoplasma gondii, disseminates through its host inside infected immune cells. We hypothesize that parasite nutrient requirements lead to manipulation of migratory properties of the immune cell. We demonstrate that 1) T. gondii relies on glutamine for optimal infection, replication and viability, and 2) T. gondii-infected bone marrow-derived dendritic cells (DCs) display both “hypermotility” and “enhanced migration” to an elevated glutamine gradient in vitro. We show that glutamine uptake by the sodium-dependent neutral amino acid transporter 2 (SNAT2) is required for this enhanced migration. SNAT2 transport of glutamine is also a significant factor in the induction of migration by the small cytokine stromal cell-derived factor-1 (SDF-1) in uninfected DCs. Blocking both SNAT2 and C-X-C chemokine receptor 4 (CXCR4; the unique receptor for SDF-1) blocks hypermotility and the enhanced migration in T. gondii-infected DCs. Changes in host cell protein expression following T. gondii infection may explain the altered migratory phenotype; we observed an increase of CD80 and unchanged protein level of CXCR4 in both T. gondii-infected and lipopolysaccharide (LPS)-stimulated DCs. However, unlike activated DCs, SNAT2 expression in the cytosol of infected cells was also unchanged. Thus, our results suggest an important role of glutamine transport via SNAT2 in immune cell migration and a possible interaction between SNAT2 and CXCR4, by which T. gondii manipulates host cell motility. |
| first_indexed | 2024-10-01T03:18:51Z |
| format | Journal Article |
| id | ntu-10356/101134 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:18:51Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/1011342023-02-28T17:05:15Z Toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through SNAT2 and CXCR4 pathways De Miguel, Zurine Manley, Nathan C. Lee, I-Ping Evans, Andrew K. Yang, Cissy Works, Melissa G. Kumar, Vineet Sapolsky, Robert M. Bogyo, Matthew School of Biological Sciences DRNTU::Science::Biological sciences The obligate intracellular parasite, Toxoplasma gondii, disseminates through its host inside infected immune cells. We hypothesize that parasite nutrient requirements lead to manipulation of migratory properties of the immune cell. We demonstrate that 1) T. gondii relies on glutamine for optimal infection, replication and viability, and 2) T. gondii-infected bone marrow-derived dendritic cells (DCs) display both “hypermotility” and “enhanced migration” to an elevated glutamine gradient in vitro. We show that glutamine uptake by the sodium-dependent neutral amino acid transporter 2 (SNAT2) is required for this enhanced migration. SNAT2 transport of glutamine is also a significant factor in the induction of migration by the small cytokine stromal cell-derived factor-1 (SDF-1) in uninfected DCs. Blocking both SNAT2 and C-X-C chemokine receptor 4 (CXCR4; the unique receptor for SDF-1) blocks hypermotility and the enhanced migration in T. gondii-infected DCs. Changes in host cell protein expression following T. gondii infection may explain the altered migratory phenotype; we observed an increase of CD80 and unchanged protein level of CXCR4 in both T. gondii-infected and lipopolysaccharide (LPS)-stimulated DCs. However, unlike activated DCs, SNAT2 expression in the cytosol of infected cells was also unchanged. Thus, our results suggest an important role of glutamine transport via SNAT2 in immune cell migration and a possible interaction between SNAT2 and CXCR4, by which T. gondii manipulates host cell motility. Published version 2014-10-28T08:21:54Z 2019-12-06T20:33:47Z 2014-10-28T08:21:54Z 2019-12-06T20:33:47Z 2014 2014 Journal Article Lee, I.-P., Evans, A. K., Yang, C., Works, M. G., Kumar, V., De Miguel, Z., et al. (2014). Toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through SNAT2 and CXCR4 pathways. PLoS One, 9(10). 1932-6203 https://hdl.handle.net/10356/101134 http://hdl.handle.net/10220/24140 10.1371/journal.pone.0109803 25299045 en PLoS One © 2014 Lee 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. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences De Miguel, Zurine Manley, Nathan C. Lee, I-Ping Evans, Andrew K. Yang, Cissy Works, Melissa G. Kumar, Vineet Sapolsky, Robert M. Toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through SNAT2 and CXCR4 pathways |
| title | Toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through SNAT2 and CXCR4 pathways |
| title_full | Toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through SNAT2 and CXCR4 pathways |
| title_fullStr | Toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through SNAT2 and CXCR4 pathways |
| title_full_unstemmed | Toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through SNAT2 and CXCR4 pathways |
| title_short | Toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through SNAT2 and CXCR4 pathways |
| title_sort | toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through snat2 and cxcr4 pathways |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/101134 http://hdl.handle.net/10220/24140 |
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