The role of Langerhans cells and dendritic cells in viral dissemination: Infection and transmission

Research output: PhD ThesisPhd-Thesis - Research and graduation internal

Abstract

Dendritic cells and Langerhans cells are antigen presenting cells and therefore critical in the initiation of immune responses to control viral infections. However, various viruses hijack the function of these immune cells for establishing infection and dissemination in the host, Thus, the cellular and molecular characteristics of dendritic cells and Langerhans cells are among the first determinants that control either viral restriction or dissemination. The research described in this thesis is focused on the different ways in which viruses exploit the function of dendritic cells and Langerhans cells for dissemination in a newly infected host. We have mainly focused on cell-to-cell transmission of different viruses (human immunodeficiency virus, Dengue virus, enterovirus A71) mediated by dendritic cells and Langerhans cells during early transmission, and we have identified various receptors and their cellular internalization pathways involved. Moreover, we have shown that external factors such as a dysbiotic human microbiome influences not only immune responses via dendritic cells, but also cell-to-cell transmission by Langerhans cells, thereby enhancing susceptibility to viruses. Our results demonstrate that the specific characteristics of dendritic cells and Langerhans cells impact the rate of viral dissemination and emphasize the significant contribution of cellular internalization pathways in cell-to-cell transmission. The mode of viral transmission is an important determinant in the approach of therapeutic strategies. Hence, progress in the understanding of early transmission events can provide alternative treatment approaches to interfere with this process or provide early diagnostics tools to identify populations at risk.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
  • Geijtenbeek, Teunis B.H., Supervisor, External person
  • Sridhar, Adithya, Co-supervisor
  • Ribeiro, C.M.S., Co-supervisor, External person
  • Geijtenbeek, Theo, Supervisor
  • Ribeiro, Carla, Co-supervisor
Award date20 Sept 2023
Print ISBNs9789493278479
Publication statusPublished - 2023

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