A novel role for SRCR proteins at the interface of maternal-fetal infections associated with neonatal sepsis

• Autor(a) principal: Silva, Maria Carolina Almeida da
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/40945
• topic: SSC5D; PRR; Placenta; Infection; Immune response; Pregnancy-associated infections; Group B streptococcus (GBS); Escherichia coli (E. coli); Immune cells

Soluble scavenger with 5 SRCR domains (SSC5D) is a member of the scavenger receptor cysteine-rich (SRCR) protein family, that functions as a pattern recognition receptor (PRR), being capable of physically interacting with Grampositive and Gram-negative bacteria. SSC5D has been identified in mice and humans, exhibiting expression in diverse structures along the mouse urogenital tract, with notable abundance in the human placenta, indicating a potential role in placental function. SSC5D-knockout (KO) mice were used to investigate the role of this protein during normal pregnancy development and in infections, particularly those associated with the genito-urinary tract and pregnancy. Our findings indicate that mice deficient in SSC5D have significantly reduced embryo weight and litter size. These results show that in the absence of the protein, the placenta undergoes dramatic modifications, including significant changes in gene expression patterns, tissue size, and structure compared to wild-type (WT) mice. Indeed, SSC5D expression is significantly elevated in WT pregnant mice at the early stages of gestation, remaining stable throughout the remaining pregnancy period, indicating its possible role and contribution to embryonic and placental development. However, the quantity and distribution of immune cells in WT and SSC5D-KO placentas showed no significant differences. We then evaluated whether SSC5D has a protective effect in the context of disease, namely in a systemic infection induced by an uropathogenic E. coli (UPEC) and found that SSC5D-KO mice are significantly more susceptible in this in vivo infection model, presenting increased bacterial burden in relevant organs. Furthermore, using an ascending disease model mimicking the natural infection route of GBS in humans showed the pivotal role of SSC5D in the mother/fetal interface in a pregnancy-associated infection. Neonates born from GBS-infected SSC5D-KO mothers displayed elevated mortality rates and higher bacterial burden in the brain, lungs, and liver compared to WT newborns, which exhibited no bacterial presence in these organs. These findings emphasize the importance of SSC5D in placental development and pregnancy. They also highlight the protein's role in promoting bacterial clearance and resolution of inflammation in pregnancy-associated infections, suggesting that SSC5D is a promising therapeutic candidate to fight infections acquired during fetal development or at birth, which are a significant cause of fetal and neonatal mortality.