Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages
© 2020, The Author(s). Macrophages play an essential role in the early immune response against Toxoplasma and are the cell type preferentially infected by the parasite in vivo. Interferon gamma (IFNγ) elicits a variety of anti-Toxoplasma activities in macrophages. Using a genome-wide CRISPR screen w...
| Main Authors: | , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2021
|
| Online Access: | https://hdl.handle.net/1721.1/135295 |
| _version_ | 1826207604931559424 |
|---|---|
| author | Wang, Yifan Sangaré, Lamba Omar Paredes-Santos, Tatiana C Hassan, Musa A Krishnamurthy, Shruthi Furuta, Anna M Markus, Benedikt M Lourido, Sebastian Saeij, Jeroen PJ |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Wang, Yifan Sangaré, Lamba Omar Paredes-Santos, Tatiana C Hassan, Musa A Krishnamurthy, Shruthi Furuta, Anna M Markus, Benedikt M Lourido, Sebastian Saeij, Jeroen PJ |
| author_sort | Wang, Yifan |
| collection | MIT |
| description | © 2020, The Author(s). Macrophages play an essential role in the early immune response against Toxoplasma and are the cell type preferentially infected by the parasite in vivo. Interferon gamma (IFNγ) elicits a variety of anti-Toxoplasma activities in macrophages. Using a genome-wide CRISPR screen we identify 353 Toxoplasma genes that determine parasite fitness in naїve or IFNγ-activated murine macrophages, seven of which are further confirmed. We show that one of these genes encodes dense granule protein GRA45, which has a chaperone-like domain, is critical for correct localization of GRAs into the PVM and secretion of GRA effectors into the host cytoplasm. Parasites lacking GRA45 are more susceptible to IFNγ-mediated growth inhibition and have reduced virulence in mice. Together, we identify and characterize an important chaperone-like GRA in Toxoplasma and provide a resource for the community to further explore the function of Toxoplasma genes that determine fitness in IFNγ-activated macrophages. |
| first_indexed | 2024-09-23T13:52:09Z |
| format | Article |
| id | mit-1721.1/135295 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:52:09Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1352952024-01-02T18:38:29Z Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages Wang, Yifan Sangaré, Lamba Omar Paredes-Santos, Tatiana C Hassan, Musa A Krishnamurthy, Shruthi Furuta, Anna M Markus, Benedikt M Lourido, Sebastian Saeij, Jeroen PJ Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research © 2020, The Author(s). Macrophages play an essential role in the early immune response against Toxoplasma and are the cell type preferentially infected by the parasite in vivo. Interferon gamma (IFNγ) elicits a variety of anti-Toxoplasma activities in macrophages. Using a genome-wide CRISPR screen we identify 353 Toxoplasma genes that determine parasite fitness in naїve or IFNγ-activated murine macrophages, seven of which are further confirmed. We show that one of these genes encodes dense granule protein GRA45, which has a chaperone-like domain, is critical for correct localization of GRAs into the PVM and secretion of GRA effectors into the host cytoplasm. Parasites lacking GRA45 are more susceptible to IFNγ-mediated growth inhibition and have reduced virulence in mice. Together, we identify and characterize an important chaperone-like GRA in Toxoplasma and provide a resource for the community to further explore the function of Toxoplasma genes that determine fitness in IFNγ-activated macrophages. 2021-10-27T20:22:50Z 2021-10-27T20:22:50Z 2020 2021-07-21T16:52:07Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135295 en 10.1038/S41467-020-18991-8 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Wang, Yifan Sangaré, Lamba Omar Paredes-Santos, Tatiana C Hassan, Musa A Krishnamurthy, Shruthi Furuta, Anna M Markus, Benedikt M Lourido, Sebastian Saeij, Jeroen PJ Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages |
| title | Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages |
| title_full | Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages |
| title_fullStr | Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages |
| title_full_unstemmed | Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages |
| title_short | Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages |
| title_sort | genome wide screens identify toxoplasma gondii determinants of parasite fitness in ifnγ activated murine macrophages |
| url | https://hdl.handle.net/1721.1/135295 |
| work_keys_str_mv | AT wangyifan genomewidescreensidentifytoxoplasmagondiideterminantsofparasitefitnessinifngactivatedmurinemacrophages AT sangarelambaomar genomewidescreensidentifytoxoplasmagondiideterminantsofparasitefitnessinifngactivatedmurinemacrophages AT paredessantostatianac genomewidescreensidentifytoxoplasmagondiideterminantsofparasitefitnessinifngactivatedmurinemacrophages AT hassanmusaa genomewidescreensidentifytoxoplasmagondiideterminantsofparasitefitnessinifngactivatedmurinemacrophages AT krishnamurthyshruthi genomewidescreensidentifytoxoplasmagondiideterminantsofparasitefitnessinifngactivatedmurinemacrophages AT furutaannam genomewidescreensidentifytoxoplasmagondiideterminantsofparasitefitnessinifngactivatedmurinemacrophages AT markusbenediktm genomewidescreensidentifytoxoplasmagondiideterminantsofparasitefitnessinifngactivatedmurinemacrophages AT louridosebastian genomewidescreensidentifytoxoplasmagondiideterminantsofparasitefitnessinifngactivatedmurinemacrophages AT saeijjeroenpj genomewidescreensidentifytoxoplasmagondiideterminantsofparasitefitnessinifngactivatedmurinemacrophages |