Parasite Fate and Involvement of Infected Cells in the Induction of CD4 and CD8 T Cell Responses to
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.
Vyšlo v časopise:
Parasite Fate and Involvement of Infected Cells in the Induction of CD4 and CD8 T Cell Responses to. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004047
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004047
Souhrn
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.
Zdroje
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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