The role of CD1a in dengue infection
<p>Dengue is one the most prevalent tropical infectious diseases. It causes a heavy healthcare burden globally, while treatment and prevention approaches are limited. Like other virus-induced diseases, T cells are considered to play an important role in the immunity against dengue virus infect...
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
2021
|
| Subjects: |
| _version_ | 1817932151371333632 |
|---|---|
| author | Yang, J |
| author2 | Ogg, G |
| author_facet | Ogg, G Yang, J |
| author_sort | Yang, J |
| collection | OXFORD |
| description | <p>Dengue is one the most prevalent tropical infectious diseases. It causes a heavy healthcare burden globally, while treatment and prevention approaches are limited. Like other virus-induced diseases, T cells are considered to play an important role in the immunity against dengue virus infection. However, compared to conventional MHC-activated T cells, the role of CD1a-restricted, lipid-specific T cells in dengue infection has not been studied.</p>
<p>The aim of this project was to investigate the role of CD1a in the immunity of dengue virus infection.</p>
<p>Human monocyte-derived dendritic cells (moDCs) were used as models to study the regulation of surface CD1a expression in the context of dengue virus infection. Components in sera derived from acute phase dengue patients were found to downregulate CD1a expression by moDCs which may in part be explained by IL-10. To investigate the effect of dengue infection on the function of CD1a-reactive T cells, polyclonal blood T cells from patients and controls, and CD1a-autoreactive T cells clone/lines were utilised. The production of IFN-γ and GM-CSF by CD1a-autoreactive T cells was reduced when co-cultured with dengue-infected presenting cells. Receptors for dengue viral entry are incompletely understood. Langerhans cells represent an early target cell for dengue virus, and express langerin, a C-type lectin which supports CD1a antigen presentation. Here, we define langerin as a novel target for dengue NS1 and E proteins in vitro, and provide data supporting an anti-viral effect of langerin engagement.</p>
<p>In summary, this thesis describes the first study of the role of CD1a in dengue virus infection. The data show that the expression of CD1a and the activity of CD1a-reactive T cells are regulated by dengue virus infection, and that langerin is a novel dengue receptor. Collectively the data implicate the CD1a pathway in dengue pathogenesis and provide insights into future therapeutic and vaccine development.</p>
|
| first_indexed | 2024-03-06T19:30:01Z |
| format | Thesis |
| id | oxford-uuid:1d22a372-85eb-4cb4-bc21-de45bfba9675 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:33:21Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | oxford-uuid:1d22a372-85eb-4cb4-bc21-de45bfba96752024-12-01T16:32:51ZThe role of CD1a in dengue infectionThesishttp://purl.org/coar/resource_type/c_db06uuid:1d22a372-85eb-4cb4-bc21-de45bfba9675ImmunologyEnglishHyrax Deposit2021Yang, JOgg, GHardman, C<p>Dengue is one the most prevalent tropical infectious diseases. It causes a heavy healthcare burden globally, while treatment and prevention approaches are limited. Like other virus-induced diseases, T cells are considered to play an important role in the immunity against dengue virus infection. However, compared to conventional MHC-activated T cells, the role of CD1a-restricted, lipid-specific T cells in dengue infection has not been studied.</p> <p>The aim of this project was to investigate the role of CD1a in the immunity of dengue virus infection.</p> <p>Human monocyte-derived dendritic cells (moDCs) were used as models to study the regulation of surface CD1a expression in the context of dengue virus infection. Components in sera derived from acute phase dengue patients were found to downregulate CD1a expression by moDCs which may in part be explained by IL-10. To investigate the effect of dengue infection on the function of CD1a-reactive T cells, polyclonal blood T cells from patients and controls, and CD1a-autoreactive T cells clone/lines were utilised. The production of IFN-γ and GM-CSF by CD1a-autoreactive T cells was reduced when co-cultured with dengue-infected presenting cells. Receptors for dengue viral entry are incompletely understood. Langerhans cells represent an early target cell for dengue virus, and express langerin, a C-type lectin which supports CD1a antigen presentation. Here, we define langerin as a novel target for dengue NS1 and E proteins in vitro, and provide data supporting an anti-viral effect of langerin engagement.</p> <p>In summary, this thesis describes the first study of the role of CD1a in dengue virus infection. The data show that the expression of CD1a and the activity of CD1a-reactive T cells are regulated by dengue virus infection, and that langerin is a novel dengue receptor. Collectively the data implicate the CD1a pathway in dengue pathogenesis and provide insights into future therapeutic and vaccine development.</p> |
| spellingShingle | Immunology Yang, J The role of CD1a in dengue infection |
| title | The role of CD1a in dengue infection |
| title_full | The role of CD1a in dengue infection |
| title_fullStr | The role of CD1a in dengue infection |
| title_full_unstemmed | The role of CD1a in dengue infection |
| title_short | The role of CD1a in dengue infection |
| title_sort | role of cd1a in dengue infection |
| topic | Immunology |
| work_keys_str_mv | AT yangj theroleofcd1aindengueinfection AT yangj roleofcd1aindengueinfection |