- Host-pathogen interplay in viral transmission and immune evasion
- Award date
- 3 April 2014
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Dendritic cell (DC) subsets and macrophages are located in mucosal tissues to identify intruding pathogens. In order to do so, these innate immune cells express pattern recognition receptors, including C-type lectin receptors (CLR) on the cell surface. Activation of these receptors promotes pathogen uptake and induces intracellular signaling, leading to immune activation. These cells and the receptors expressed are therefore pivotal in the interplay between pathogen and host. This thesis describes the events following initial contact between pathogens (measles virus (MV), HIV-1 and Candida albicans) and innate immune cells, with a focus on recognition of pathogens and subsequent innate signaling that affects infection and immunity.
Results show that DCs are targeted by MV early in infection in vivo. In particular expression of CLR DC-SIGN by DCs has major effects on viral infections, as its function is subverted by MV in multiple ways to promote viral dissemination - by enhancing cellular infection and transmission to lymphocytes as well as via signaling, which suppresses RIG-I-like receptor-mediated antiviral responses.
Langerhans cells are the first cells to encounter HIV-1. LCs are infected by both X4 and R5 viruses, but only transmit R5 HIV-1 to T lymphocytes, implying that LCs play a crucial role in R5 selection, the predominantly transmitted HIV-1 strain.
These data give more insight in pathogen recognition by innate immune cells and underline the specific characteristics of the different cell types.
- Research conducted at: Universiteit van Amsterdam
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