Parasite Fate and Involvement of Infected Cells in the Induction of CD4+ and CD8+ T Cell Responses to Toxoplasma gondii
| العنوان: | Parasite Fate and Involvement of Infected Cells in the Induction of CD4+ and CD8+ T Cell Responses to Toxoplasma gondii |
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| المؤلفون: | Gretchen Harms Pritchard, Marion Pepper, Christopher A. Hunter, L. David Sibley, Morgan A. Reuter, Christopher D. Dupont, Sagie Wagage, Elizabeth M. Selleck, Anita A. Koshy, Michael Alexander Leney-Greene, David A. Christian, Michael R. Betts |
| المصدر: | PLoS Pathogens PLoS Pathogens, Vol 10, Iss 4, p e1004047 (2014) |
| بيانات النشر: | Public Library of Science, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, Immunofluorescence, Pathogenesis, Protozoology, CD8-Positive T-Lymphocytes, Pathology and Laboratory Medicine, Toxoplasma Gondii, Major Histocompatibility Complex, White Blood Cells, Mice, Animal Cells, Medicine and Health Sciences, Cytotoxic T cell, lcsh:QH301-705.5, Immune Response, Protozoans, Immunity, Cellular, biology, T Cells, Animal Models, Natural killer T cell, Vaccination and Immunization, 3. Good health, Cell biology, medicine.anatomical_structure, Infectious Diseases, Medical Microbiology, Host-Pathogen Interactions, Interleukin 12, Cellular Types, Toxoplasma, Toxoplasmosis, Research Article, lcsh:Immunologic diseases. Allergy, T cell, Immune Cells, Antigen presentation, Immunology, Antigen-Presenting Cells, Mouse Models, Research and Analysis Methods, Immune Suppression, Microbiology, Immune Activation, Model Organisms, Virology, Genetics, medicine, Parasitic Diseases, Animals, Antigen-presenting cell, Immunoassays, Molecular Biology, Immunity to Infections, Microbial Pathogens, CD40, Blood Cells, Protozoan Infections, Protozoan Models, Immunity, Organisms, Biology and Life Sciences, Cell Biology, Dendritic Cells, Acquired Immune System, Parasitic Protozoans, lcsh:Biology (General), Immune System, biology.protein, Myeloid-derived Suppressor Cell, Immunologic Techniques, Clinical Immunology, Parasitology, lcsh:RC581-607 |
| الوصف: | 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. Author Summary CD4+ and CD8+ T cells are critical for controlling many infections. To generate a T cell response during infection, T cells must encounter the microbial peptides that they recognize bound to MHC molecules on the surfaces of other cells, such as dendritic cells. It is currently unclear how dendritic cells acquire the antigens they present to T cells during infection with many intracellular pathogens. It is possible that these antigens are phagocytosed and processed by dendritic cells, or antigens may be presented by cells that are infected by pathogens such as Toxoplasma gondii, which invades host cells independently of phagocytosis. To differentiate these pathways, we developed a novel technique to track the fate of T. gondii in vivo that distinguishes actively infected cells from those that phagocytosed parasites. This technique was used to examine each of these cell populations. We also used pharmacological inhibitors of parasite invasion, and the transfer of sort-purified infected or uninfected dendritic cells and macrophages to determine what roles phagocytosis and active invasion have in the initiation of T cell responses. Our results demonstrate that phagocytosis of parasites is not sufficient to induce CD4+ or CD8+ T cell responses, whereas infected cells are critical for this process. |
| اللغة: | English |
| تدمد: | 1553-7374 1553-7366 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fabc119c75eea62a2ebb4535ba5bf80dTest http://europepmc.org/articles/PMC3983043Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fabc119c75eea62a2ebb4535ba5bf80d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 15537366 |
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