Fig. 8
Pictorial summary from the findings. a Under the influences of B16 melanoma, murine dendritic cells secrete IL-10 (anti-inflammatory) and IL-12 (IL-12p70, mainly depending on its constituent IL-12p35 from Il12a gene) (pro-inflammatory) at their corresponding tumor-imposed levels. Neem Leaf Glycoprotein (NLGP) binds to Dectin-1 receptors, on these cells and initiates an intracellular signal transduction cascade, which reduces IL-10 secretion and simultaneously increases secretion level of IL-12p70 from these cells. As this signal intensifies gradually, reduction of IL-10 and enhancement of IL-12p35 becomes prominent at their secretory levels, thereby initiating type 1 immune-commitment. However, intracellularization of NLGP might play a role in attenuation of this signal later on, which eventually would terminate this signal. b As the signal initiated by NLGP-Dectin-1 receptor association within these dendritic cells and its intracellular transduction was studied, it was found that upon proximity to these cells, NLGP binds Dectin-1 receptors through its protruded β-D-Glucan chains. Consequently, a signal is delivered to CARD9, through phosphorylation of PKCδ (not shown in this representation). CARD9, on being phosphorylated attaches itself to Bcl10 and MALT1, forming the trimolecular CARD9-Bcl10-MALT1 (CBM) complex. This complex activates NFκB in the canonical way. Thus, upon phosphorylation, ubiquitination and subsequent proteasomal degradation of the corresponding IκB components, the canonical NFκB dimers, p65:p50 and p50:p50 translocate into the nuclei of these cells. Within the nuclei the enhancer p65:p50 dimer raises Il12a gene’s transcription, whereas the repressor dimer p50:p50 decreases the transcription rate of the Il10 gene. Following translation, modifications, secretion etc., such regulated levels of these cytokines are reflected as an uprise in secretion of the pro-inflammatory cytokine IL-12p70, along with depleted secretion of the anti-inflammatory IL-10 secretion from these dendritic cells. c Diagrammatic legend of the visual perspectives in (a) and (b)