Host-Pathogen Interactions During Pregnancy: Mechanisms of Maternal and Fetal Immunity

Yael Alippe^1*Vanesa Hauk^2*Gil Mor^3*DAIANA M. VOTA^2*

• ¹Washington University in St. Louis, St. Louis, United States
• ²CONICET Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
• ³Wayne State University, Detroit, United States

spontaneous abortion, preterm birth, and congenital abnormalities. Despite significant 5 progress, many aspects of immune responses during pregnancy and the mechanisms driving 6 infection-induced adverse outcomes remain unclear. This Research Topic provides novel 7 insights into these complex interactions, offering a deeper understanding of maternal-fetal 8 immunity and highlighting potential therapeutic avenues. 9A critical aspect of maintaining immune homeostasis during pregnancy is the modulation of 10 inflammation in response to physiological or pathological challenges. Krupa et al. provide 11 evidence that B lymphocytes play a crucial role in fetal tolerance through secretion of soluble 12 CD83 (sCD83), an anti-inflammatory mediator. Upon bacterial stimulation, decidual and 13 peripheral B cells exhibit distinct capacities for sCD83 secretion, modulated by pregnancy-14 associated hormones such as estradiol (E2), progesterone (P4), transforming growth factor-15 beta 1 (TGF-β1), and human chorionic gonadotropin (hCG). While these hormones enhance 16 lipopolysaccharide (LPS)-induced CD83 expression, glucocorticoids inhibit this process, 17 underscoring the complex hormonal regulation that fine-tunes immune responses during 18In line with this hormone-immune interplay, Chen et al. explore the role of placental alkaline 20 phosphatase (ALPP), an enzyme highly expressed during pregnancy. Their studies using 21 transgenic mouse models reveal that increased ALPP expression heightens susceptibility to 22 LPS-induced sepsis and disrupts adaptive immune responses. This dual function of ALPP-23 mediating both tolerance and defense-highlights the intricate balance required for healthy 24 pregnancy outcomes, particularly in bacterial infection contexts. sepsis and maternal infection trends from 1990 to 2019. Their findings reveal a significant 44 overall decrease in global incidence and mortality rates but highlight persistent regional 45 disparities, particularly in the African region. This disparity emphasizes the urgent need for 46 targeted healthcare policies at global, regional, and national levels aimed at equitable access 47 to maternal care and improved management of pregnancy-related infections worldwide. 48