<p>The cellular immune response is not only affected by endogenous cytokines or mediators but also affected by exogenous chemical products from food. Human blood leukocytes express members of chemosensory taste receptors such as sweet and umami taste receptors (TAS1Rs) and bitter taste receptors (TAS2Rs). These ectopic taste receptors have been found to sense irritants or bacterial lipopolysaccharides and activate innate immunity. Saccharin, an artificial sweetener, can modulate the cellular immune response via the leukocytic taste receptors. The study aimed to investigate the in vitro effect of saccharin on the function of isolated polymorphonuclear neutrophils (PMNs) in the blood by stimulating sweet taste receptors. Chemotaxis and transmigration assays were measured along with transcriptional profiling of selected neutrophil inflammatory chemokines (CXCL1, CCL2 and CCL26) and chemokine receptors (IL8R and CCR4) following in vitro stimulation by saccharin through siRNA knockdown and RT-qPCR. Saccharin was found to activate chemotaxis in isolated human leukocytes and also to activate PMN migration in a concentration-dependent manner. It was found that siRNA against TAS1R2 or TAS1R3 suppressed PMN migration towards saccharin. On the other hand, no loss of migration occurred in PMN transfected with siRNA against TAS1R1 or in non-siRNA transfected PMNs. Incubation of PMNs with saccharin resulted in a significant upregulation of chemokine and chemokine receptor transcript levels.&#xa0;Our study indicates that saccharin can orchestrate innate immunity by stimulating their cognate taste receptors in the peripheral blood PMNs by signaling chemokines and their receptors.</p>