Understanding the mechanisms of host cell activation may provide insight into the pathogenesis of these infections. We are using different target cells (i.e. endothelial cell lines, elutriated blood mononuclear cells, whole blood assays) to characterize the early gene and protein expression associated with fungal- related molecules (i.e. beta glucans, zymosan, and laminarin). ? ? We have evaluated the cell activation expression with immunoassays, Taq-Man probes for specific target genes (i.e. IL-6, 8, MCP) as well as RT-PCR arrays which allow us to profile 84 genes per sample to assess the interactions of the different fungal related molecules. For example, stimulation of monocytes with laminarin, a low molecular weight glucan, is associated with a mixture of inhibitory and stimulatory gene expression in the toll receptor pathway. Pretreatment with laminarin also has a major effect on inhibiting monocyte activation by either curdlan (a beta 1,3, glucan) or zymosan. We are continuing to evaluate the signaling pathways using these methodologies in order to elucidate host inflammatory mechanisms activated by fungal related molecules.
