Modulation of thelper polarization by GM-CSF and the dectin-1 ligand, curdlan.
Date of Issue2011
School of Biological Sciences
Dendritic cells (DCs) work as antigen presenting cells that help in the polarization of CD4 T cells into effector and regulatory subsets. Pathogen recognition receptors (PRRs) like Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) on DCs recognise pathogen-associated molecular patterns (PAMPS) on pathogens. Activation of DCs by TLRs and CLRs agonists can promote Th1 and Th17 anti-fungal responses. CLR Dectin-1 is a specific receptor for 1, 3-glucans. Its activation can induce cytokines responsible for polarization of Th1 and Th17 cells. Granulocyte macrophage colony stimulating factor (GM-CSF) is shown to enhance expression of dectin-1 in DCs. Thus, this study looks into the effect of GM-CSF and dectin-1 specific agonist-curdlan on their role in modulating differentiation of T helper cells. Various TLR agonists were also used in this study. GM-CSF resulted in the increased production of pro-inflammatory cytokines IL-6, IL-12 and IFN necessary for polarization of Th1 and Th17 cells. GM-CSF was able to promote a higher population of Th1 and Th17 cells to some extent. Curdlan was able to elicit Th1 and Th17 responses however; we found that other TLR agonists, for example CpG B, were stronger promoters of Th1 and Th17 anti-fungal immunity.
Final Year Project (FYP)
Nanyang Technological University