Distinct maternofetal immune signatures delineate preterm birth onset following urinary tract infection

Preterm birth is the leading cause of infant mortality resulting in over one million neonatal deaths annually. Maternal urinary tract infection (UTI) during pregnancy increases risk for preterm birth; however, biological processes mediating UTI-associated preterm birth are not well-described. We established a murine maternal UTI model in which challenge with uropathogenic E. coli resulted in preterm birth in about half of dams. Dams experiencing preterm birth displayed excessive bladder inflammation and altered uteroplacental T cell polarization compared to non-laboring infected dams, with no differences in bacterial burdens. Additional factors associated with preterm birth included higher proportions of male fetuses and lower maternal serum IL-10. Furthermore, exogenous maternal IL-10 treatment absolved UTI-associated preterm birth but contributed to fetal growth restriction in this model. Overall design: 129/sv dams and nonpregnant controls were transurethrally infected with 5e7 UTI89 on E13.5. Four hours later, dams were euthanized and bladder, placenta, and uterus were resected. Total RNA was extracted using Rneasy Plus mini kits (Qiagen 74134). mRNA was purified from total RNA using poly-T beads, then cDNA was synthesized and sequenced on an Illumina NovaSeq 6000 sequencer. Differential gene expression was determined using DESeq2.