The induction of preterm labor in rhesus macaques is determined by the strength of immune response to intrauterine infection.
Monica CappellettiPietro PresicceFeiyang MaParanthaman S KannanLisa A MillerMatteo PellegriniMyung S SimAlan H JobeSenad DivanovicSing Sing WayClaire A ChougnetSuhas G KallapurPublished in: PLoS biology (2021)
Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor (PTL). However, IUI does not invariably cause PTL. We hypothesized that quantitative and qualitative differences in immune response exist in subjects with or without PTL. To define the triggers for PTL, we developed rhesus macaque models of IUI driven by lipopolysaccharide (LPS) or live Escherichia coli. PTL did not occur in LPS challenged rhesus macaques, while E. coli-infected animals frequently delivered preterm. Although LPS and live E. coli both caused immune cell infiltration, E. coli-infected animals showed higher levels of inflammatory mediators, particularly interleukin 6 (IL-6) and prostaglandins, in the chorioamnion-decidua and amniotic fluid (AF). Neutrophil infiltration in the chorio-decidua was a common feature to both LPS and E. coli. However, neutrophilic infiltration and IL6 and PTGS2 expression in the amnion was specifically induced by live E. coli. RNA sequencing (RNA-seq) analysis of fetal membranes revealed that specific pathways involved in augmentation of inflammation including type I interferon (IFN) response, chemotaxis, sumoylation, and iron homeostasis were up-regulated in the E. coli group compared to the LPS group. Our data suggest that the intensity of the host immune response to IUI may determine susceptibility to PTL.
Keyphrases
- escherichia coli
- inflammatory response
- immune response
- single cell
- rna seq
- anti inflammatory
- oxidative stress
- dendritic cells
- toll like receptor
- preterm birth
- low birth weight
- biofilm formation
- lps induced
- gestational age
- machine learning
- klebsiella pneumoniae
- deep learning
- electronic health record
- mesenchymal stem cells
- pseudomonas aeruginosa
- mass spectrometry
- multidrug resistant