Rapid release of sepsis markers heparin-binding protein and calprotectin triggered by anaerobic cocci poses an underestimated threat

Abstract

Objectives: Gram-positive anaerobic cocci (GPAC) are often regarded as harmless commensals associated with skin and mucosal surfaces. Investigations regarding these bacterial species often concern clinical case reports. In immunocompromised individuals, in the presence of comorbidities, such as diabetes or due to breach of skin barriers, the GPAC can cause infections. Nonetheless, information on the direct impact of these bacteria on blood-derived immune cells remains sparse.

Methods: Heat-inactivated GPAC strains (Finegoldia magna, Peptoniphilus harei, Parvimonas micra and Anaerococcus spp.) were incubated with whole blood from healthy human donors for 15 min or 4 h. Following the incubation, plasma samples were collected and analysed by ELISA for secretion of heparin-binding protein (HBP), myeloperoxidase (MPO), calprotectin (S100A8/S100A9; MRP-8/MRP-14) and TNFα as markers for immune cell activation.

Results: The direct interaction of GPAC with whole blood demonstrated a significant effect on the immune response. Incubation of the bacterial strains with blood triggered rapid secretion of sepsis markers HBP and calprotectin, as well as the pro-inflammatory cytokine TNFα. Due to lack of MPO secretion at the early time point, it was hypothesised that the early HBP originated from the neutrophil secretory vesicles. Trypsin-treatment of the bacteria slightly reduced the HBP release, suggesting an involvement of bacterial surface proteins.

Conclusions: The findings suggest that GPAC species isolated from blood might pose an underestimated threat to the host. Further research concerning anaerobic cocci in direct interaction with the human host is therefore needed and justified.