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[Bacterial pathogen associated molecular pattern and superantigens indirectly induce the accelerated death of bovine
Hans-Joachim Schuberth1, Julia Dahnke, Wolfgang Leibold
1Arbeitsgruppe Immunologie,Tierärztliche Hochschule, Hannover. Hans-Joachim.Schubert@tiho-hannover.de
Abstract:
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.
Insights
Pathogen-associated molecular patterns (PAMPs) and superantigens indirectly reduce bovine neutrophil survival. These immune stimulators, particularly CpG motifs, accelerate PMN death when interacting with mononuclear cells or macrophages.
Area of Science:
- Immunology
- Cell Biology
Background:
- Pathogen-associated molecular patterns (PAMPs) and bacterial superantigens are known to affect mononuclear cells (MNC) and macrophages.
- The impact of PAMPs, specifically non-methylated CpG motifs, on neutrophilic granulocytes (PMN) has received less attention.
Purpose of the Study:
- To investigate the direct and indirect effects of PAMPs and the superantigen SEA on the survival rate of bovine PMN.
- To determine if CpG motifs, LPS, and SEA influence PMN viability alone or in combination with MNC or macrophages.
Main Methods:
- Exposure of pure bovine PMN to various PAMPs (CpG motifs, GpC motif, LPS) and SEA.
- Co-culture experiments involving PMN with MNC or in vitro generated macrophages (MdM).
- Assessment of PMN viability following stimulation with single agents or combinations thereof, comparing autologous and allogeneic settings.
Main Results:
- Pure PMN viability was not affected by CpG motifs, GpC motif, LPS, or SEA alone.
- In the presence of MNC or MdM, these stimuli induced accelerated PMN death.
- Combinations of CpG motifs with LPS or SEA showed additive or supra-additive effects, reducing PMN viability to 28-36% in MNC/PMN co-cultures.
- Both the stimulated MNC/MdM population and the individual state of PMN influenced the extent of PMN death.
Conclusions:
- CpG motifs, other PAMPs, and superantigens indirectly reduce the viability of bovine neutrophilic granulocytes.
- These interactions diminish the functional capacity of PMN, a crucial effector cell population.
- The combined action of PAMPs and superantigens with MNC/macrophages significantly impacts PMN survival.
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