Sarcletti Fabien, Dijmarescu Marco, Eigenschink Michael, Wukowits Nadja, Oehler Barbara, Mayer Tanja, Pell Sarah, Tandecki Anastasia, Seki David, Spittler Andreas, Berry David, Berger Angelika, Wisgrill Lukas
Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria.
Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria.
Eur J Immunol. 2025 Apr;55(4):e202451538. doi: 10.1002/eji.202451538.
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.
肠道微生物群与免疫系统紧密相连，影响着早期大脑发育。脑源性神经营养因子（BDNF）对神经元发育至关重要，已被证明由某些免疫细胞产生。然而，在细菌抗原和代谢产物刺激过程中BDNF的调节仍不清楚。我们研究了细菌衍生的抗原和代谢产物对人外周血单核细胞（PBMC）中BDNF分泌的影响。虽然在刺激过程中BDNF水平发生了变化，但PBMC中BDNF的特定细胞来源尚不确定。单核细胞的阳性磁分选消除了刺激物诱导的BDNF分泌，并减少了单核细胞 - 血小板聚集体。相反，血小板计数升高显著增加了BDNF水平，表明血小板在与单核细胞相互作用并暴露于细菌抗原时，可能是PBMC培养物中BDNF的主要来源。如前所述，血小板是循环外周血BDNF的关键来源。我们的研究结果强调了微生物刺激期间免疫血细胞复合物之间的相互作用在调节BDNF水平中的重要性。这突出了研究此类相互作用以更好地理解早期肠道 - 脑轴的必要性。
