GSE174689
Hofbauer cells spread Listeria monocytogenes among placental cells and undergo pro-inflammatory reprogramming while retaining production of tolerogenic factors
Pregnant women are highly susceptible to infection by the bacterial pathogen Listeria monocytogenes leading to miscarriage, premature birth, and neonatal infection. It is thought that L. monocytogenes breaches the placental barrier by infecting trophoblasts at the maternal interface. However, the fate of L. monocytogenes within the chorionic villi and how infection reaches the fetus are unsettled. Hofbauer cells (HBCs) are fetal placental macrophages and the only leukocytes residing in healthy chorionic villi, forming a last immune barrier protecting fetal blood from infection. Little is known about HBCs' antimicrobial responses to pathogens. Here, we present the first study of L. monocytogenes interactions with human HBCs isolated from healthy term placentas. Control untreated (5 h and 24 h) HBCs, 24 h LPS/IFNgamma-stimulated, and 5 h and 24 h L. monocytogenes-infected HBCs, were lysed with TRIzol. RNA was isolated followed by on-column DNase treatment and ribo-depletion. RNA-seq libraries were made, pooled, and sequenced on an Illumina NovaSeq SP flow cell in paired-end 150 bp format to a read yield between 70 – 80 million reads (equivalent to 35 – 40 million clusters). The RNA-seq data analysis showed that HBCs undergo pro-inflammatory reprogramming upon L. monocytogenes infection and following stimulation by the potent M1-polarizing agents LPS/IFNgamma. Of particular interest, infected HBCs also upregulated genes encoding numerous pro-inflammatory chemokines known to promote placental infiltration by maternal leukocytes. However, HBCs maintained expression of a collection of tolerogenic genes accompanied by secretion of tolerogenic cytokines, consistent with their tissue homeostatic role in prevention of fetal rejection. Overall design: 12 samples from 4 different conditions with 3 replicates per sample. Each sample divided across 2 sequencing lanes. Conditions were compared pairwise