The immune system exists in a delicate equilibrium between inflammatory responses and tolerance. This unique feature allows the immune system to recognize and respond to potential threats in a controlled but normally limited fashion thereby preventing a destructive overreaction against healthy tissues. While the adaptive immune system was the major research focus concerning activation vs. tolerance in the immune system more recent findings suggest that cells of the innate immune system are important players in the decision between effective immunity and induction of tolerance or immune inhibition. Among immune cells of the innate immune system dendritic cells (DCs) have a special function linking innate immune functions with the induction of adaptive immunity. DCs are the primary professional antigen presenting cells (APCs) initiating adaptive immune responses. They belong to the hematopoietic system and arise from CD34+ stem cells in the bone marrow. Particularly in the murine system two major subgroups of DCs, namely myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) can be distinguished. DCs are important mediators of innate and adaptive immunity mostly due to their remarkable capacity to present processed antigens via major histocompatibility complexes (MHC) to T cells and B cells in secondary lymphoid organs. A large body of literature has been accumulated during the last two decades describing which role DCs play during activation of T cell responses but also during the establishment and maintenance of central tolerance (Steinman et al., 2003). While the concept of peripheral tolerance has been clearly established during the last years, the role of different sets of DCs and their particular molecular mechanisms of immune deviation has not yet fully been appreciated. In this review we summarize accumulating evidence about the role of regulatory DCs in situations where the balance between tolerance and immunogenicity has been altered leading to pathologic conditions such as chronic inflammation or malignancies.

The presence of neutralizing antibodies against SARS-CoV-2 correlates with protection against infection and severe COVID-19 disease courses. Understanding the dynamics of antibody development against the SARS-CoV-2 virus is important for recommendations on vaccination strategies and on control of the COVID-19 pandemic. This study investigates the dynamics and extent of α-Spike-Ab development by different vaccines manufactured by Johnson & Johnson, AstraZeneca, Pfizer-BioNTech and Moderna. On day 1 after vaccination, we observed a temporal low-grade inflammatory response. α-Spike-Ab titers were reduced after six months of vaccination with mRNA vaccines and increased 14 days after booster vaccinations to a maximum that exceeded titers from mild and critical COVID-19 and Long-COVID patients. Within the group of critical COVID-19 patients, we observed a trend for lower α-Spike-Ab titers in the group of patients who survived COVID-19. This trend accompanied higher numbers of pro-B cells, fewer mature B cells and a higher frequency of T follicular helper cells. Finally, we present data demonstrating that past infection with mild COVID-19 does not lead to long-term increased Ab titers and that even the group of previously infected SARS-CoV-2 patients benefit from a vaccination six months after the infection.

Objective An increasing number of studies show the importance of brain-derived neurotrophic factor (BDNF) acting at the feto-placental interface, however, only a few studies describe BDNF levels in amniotic fluid (AF). Methods In this cross-sectional, prospective study, 109 maternal blood-amniotic fluid pairs (including 66 maternal blood-fetal-blood-amniotic fluid trios) were analyzed. BDNF concentrations were measured with a commercially available immunoassay. Results In 71 AF from 109 samples, AF-BDNF concentrations were below the lowest limit of Quantitation (LLoQ) of 1.19 pg/ml (group A), leaving 38 samples with measurable BDNF concentrations (group B). Patients in group A showed significantly higher maternal BMI before pregnancy (mean±SD 26.3± 6.7 (kg/m2) vs. 23.8 ±4.5 (kg/m2) p = 0.04) and lower maternal blood BDNF concentrations than the other group (mean±SD 510.6 ± 554.7 pg/ml vs. mean±SD 910.1± 690.1 pg/ml; p<0.0001). Spearman correlation showed a negative correlation between maternal BMI before pregnancy and maternal BDNF concentrations (r = -0.25, p = 0.01). Conclusion Our study is the first to correlate AF-BDNF samples with the corresponding maternal and fetal blood-BDNF samples. The significant negative correlation between maternal BMI before pregnancy and maternal BDNF and AF-BDNF concentrations below the limit of detection has to be evaluated in further studies.

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The Objective of our study was to investigate the influence of dietary (dGDM) and insulin-dependent (iGDM) gestational diabetes (GDM) on BDNF blood levels of corresponding maternal-neonatal pairs and compare them to pregnancies unaffected by GDM. Blood samples from 293 maternal-neonatal pairs were analyzed. Statistical analysis was performed using multiple regression analysis for association of log-transformed maternal and neonatal BDNF levels in relation to GDM, gestational age, neonatal sex, and mode of delivery. This was followed by a 2:1 matching of healthy and diabetic pairs. Maternal and neonatal BDNF levels were lowest in the iGDM group, followed by the dGDM group and healthy controls (maternal: healthy 665 ± 562 (26–2343) pg/mL vs. dGDM 593 ± 446 (25–1522) pg/mL vs. iGDM 541 ± 446 (68–2184) pg/mL; neonate: healthy 541 ± 464 (9.5–2802) pg/mL vs. dGDM 375 ± 342 (1–1491) pg/mL vs. iGDM 330 ± 326 (47–1384) pg/mL). After multiple regression analysis and additional 2:1 matching neonatal log-BDNF was significantly lower (−152.05 pg/mL, p = 0.027) in neonates of mothers with GDM compared to healthy pairs; maternal log-BDNF was also lower (−79.6 pg/mL), but did not reach significance. Our study is the first to analyze BDNF in matched maternal-neonatal pairs of GDM patients compared to a metabolically unaffected control group.