- C-type lectin signaling in dendritic cells: molecular control of antifungal inflammation
- Award date
- 5 June 2014
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Fungal pathogens represent a continuous and increasing danger to the human host. For design of novel preventive and therapeutic interventions to fungal infection, a concise understanding of the molecular mechanisms by which the immune system elicits antifungal inflammation is of utmost importance.
In this thesis, we have addressed the roles of C-type lectin receptors (CLRs) dectin-1, dectin-2 and mincle and how these receptors collaborate in ‘shaping’ an ensuing antifungal immune response. These studies have revealed markedly distinct modes of ‘action’ during polarization of the effector CD4+ T cell response. From our studies a model is emerging in which dectin-1 as an ‘inducer’ fuels T helper (TH) polarization, but that the overall outcome of the inflammatory response -whether protective or not- is dictated by ‘modulating’ receptors such as dectin-2 and mincle, which by themselves are incapable of inducing the response. Our attempt to understand (part of) the molecular events that underlie their functional specialization has led to novel insights into how expression of T helper cell-polarizing cytokines by dendritic cells (DCs) is transcriptionally regulated or dysregulated, but also to the characterization of the signal transduction pathways and molecular mechanisms operating downstream dectin-2 and mincle. Thus, studying these receptors has provided new insights into human antifungal immunity.
- Research conducted at: Universiteit van Amsterdam