Bacterial pathogen associated molecular pattern and superantigens indirectly induce the accelerated death of bovine neutrophilic granulocytes

Pathogen associated molecular patterns (PAMPs) and bacterial superantigens have many effects on mononuclear cells (MNC) and macrophages. Influences on neutrophilic granulocytes (PMN), especially by non methylated CpG motifs, gained less attention. Here we investigated whether PAMPs and the superantigen SEA have a direct or indirect influence on the survival rate of bovine PMN. Different CpG motifs, a reverse GpC motif, Lipopolysaccharide (LPS) and SEA did not result in a loss of viability of pure PMN. In the presence of MNC or in vitro generated macrophages (MdM), however, they induced an accelerated dying of PMN. The simultaneous stimulation of MNC/MdM with combinations of CpG motifs and LPS or SEA resulted in an additive or over additive effect: compared to control set ups, only 28-36% of the PMN remained viable in SEA/CpG stimulated MNC/PMN cocultures. Comparing autologous with allogeneic MNC/PMN or MdM/PMN cocultures, it showed up that not only the stimulated MNC or MdM population but also the individual reaction state of the PMN have an influence on the degree of PMN dying. Taken together, CpG motifs and other PAMPs as well as superantigens act in concert to reduce indirectly the viability of neutrophilic granulocytes and hence the functional capacity of an important effector cell population.