Monocyte‐Platelet Aggregates Are Major Source of BDNF after Bacterial Stimulation of Human Peripheral Blood Immune Cells

The gut microbiota and the immune system are closely connected, influencing early-life brain development. Brain-derived neurotrophic factor (BDNF), crucial for neuronal development, has been demonstrated to be produced by certain immune cells. However, the modulation of BDNF during bacterial antigen and metabolite challenge remains elusive. We investigate the effects of bacterial-derived antigens and metabolites on BDNF secretion in human PBMCs. Although BDNF levels were altered during stimulation, a specific cellular origin of BDNF within PBMCs was indeterminate. Positive magnetic separation of monocytes eliminated both the stimulant-induced BDNF secretion and reduced monocyte-platelet aggregates. Conversely, elevated platelet counts significantly increased BDNF levels, indicating that platelets, when interacting with monocytes and exposed to bacterial antigens, are likely the dominant source of BDNF in PBMC cultures. As previously described, platelets are a crucial source of circulating peripheral blood BDNF. Our findings emphasize the importance of the interplay between immune-blood cell complexes during microbial stimulation in regulating BDNF levels. This highlights the necessity of investigating such interactions to better understand the early-life gut-brain axis.