Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii.
During infection with the intracellular parasite Toxoplasma gondii, the presentation of parasite-derived antigens to CD4+ and CD8+ T cells is essential for long-term resistance to this pathogen. Fundamental questions remain regarding the roles of phagocytosis and active invasion in the events that l...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-04-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3983043?pdf=render |
| _version_ | 1818249067377983488 |
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| author | Christopher D Dupont David A Christian Elizabeth M Selleck Marion Pepper Michael Leney-Greene Gretchen Harms Pritchard Anita A Koshy Sagie Wagage Morgan A Reuter L David Sibley Michael R Betts Christopher A Hunter |
| author_facet | Christopher D Dupont David A Christian Elizabeth M Selleck Marion Pepper Michael Leney-Greene Gretchen Harms Pritchard Anita A Koshy Sagie Wagage Morgan A Reuter L David Sibley Michael R Betts Christopher A Hunter |
| author_sort | Christopher D Dupont |
| collection | DOAJ |
| description | During infection with the intracellular parasite Toxoplasma gondii, the presentation of parasite-derived antigens to CD4+ and CD8+ T cells is essential for long-term resistance to this pathogen. Fundamental questions remain regarding the roles of phagocytosis and active invasion in the events that lead to the processing and presentation of parasite antigens. To understand the most proximal events in this process, an attenuated non-replicating strain of T. gondii (the cpsII strain) was combined with a cytometry-based approach to distinguish active invasion from phagocytic uptake. In vivo studies revealed that T. gondii disproportionately infected dendritic cells and macrophages, and that infected dendritic cells and macrophages displayed an activated phenotype characterized by enhanced levels of CD86 compared to cells that had phagocytosed the parasite, thus suggesting a role for these cells in priming naïve T cells. Indeed, dendritic cells were required for optimal CD4+ and CD8+ T cell responses, and the phagocytosis of heat-killed or invasion-blocked parasites was not sufficient to induce T cell responses. Rather, the selective transfer of cpsII-infected dendritic cells or macrophages (but not those that had phagocytosed the parasite) to naïve mice potently induced CD4+ and CD8+ T cell responses, and conferred protection against challenge with virulent T. gondii. Collectively, these results point toward a critical role for actively infected host cells in initiating T. gondii-specific CD4+ and CD8+ T cell responses. |
| first_indexed | 2024-12-12T15:30:36Z |
| format | Article |
| id | doaj.art-2977843c3cf144dca58b9f44dc6e611a |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-12T15:30:36Z |
| publishDate | 2014-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-2977843c3cf144dca58b9f44dc6e611a2022-12-22T00:20:08ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-04-01104e100404710.1371/journal.ppat.1004047Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii.Christopher D DupontDavid A ChristianElizabeth M SelleckMarion PepperMichael Leney-GreeneGretchen Harms PritchardAnita A KoshySagie WagageMorgan A ReuterL David SibleyMichael R BettsChristopher A HunterDuring infection with the intracellular parasite Toxoplasma gondii, the presentation of parasite-derived antigens to CD4+ and CD8+ T cells is essential for long-term resistance to this pathogen. Fundamental questions remain regarding the roles of phagocytosis and active invasion in the events that lead to the processing and presentation of parasite antigens. To understand the most proximal events in this process, an attenuated non-replicating strain of T. gondii (the cpsII strain) was combined with a cytometry-based approach to distinguish active invasion from phagocytic uptake. In vivo studies revealed that T. gondii disproportionately infected dendritic cells and macrophages, and that infected dendritic cells and macrophages displayed an activated phenotype characterized by enhanced levels of CD86 compared to cells that had phagocytosed the parasite, thus suggesting a role for these cells in priming naïve T cells. Indeed, dendritic cells were required for optimal CD4+ and CD8+ T cell responses, and the phagocytosis of heat-killed or invasion-blocked parasites was not sufficient to induce T cell responses. Rather, the selective transfer of cpsII-infected dendritic cells or macrophages (but not those that had phagocytosed the parasite) to naïve mice potently induced CD4+ and CD8+ T cell responses, and conferred protection against challenge with virulent T. gondii. Collectively, these results point toward a critical role for actively infected host cells in initiating T. gondii-specific CD4+ and CD8+ T cell responses.http://europepmc.org/articles/PMC3983043?pdf=render |
| spellingShingle | Christopher D Dupont David A Christian Elizabeth M Selleck Marion Pepper Michael Leney-Greene Gretchen Harms Pritchard Anita A Koshy Sagie Wagage Morgan A Reuter L David Sibley Michael R Betts Christopher A Hunter Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii. PLoS Pathogens |
| title | Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii. |
| title_full | Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii. |
| title_fullStr | Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii. |
| title_full_unstemmed | Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii. |
| title_short | Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii. |
| title_sort | parasite fate and involvement of infected cells in the induction of cd4 and cd8 t cell responses to toxoplasma gondii |
| url | http://europepmc.org/articles/PMC3983043?pdf=render |
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