The induction of preterm labor in rhesus macaques is determined by the strength of immune response to intrauterine infection

Monica Cappelletti, Pietro Presicce, Ma Feiyang, Paranthaman Senthamaraikannan, Lisa A. Miller, Matteo Pellegrini, Myung S. Sim, Alan H. Jobe, Senad Divanovic, Sing Sing Way, Claire A. Chougnet, Suhas G. Kallapur

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere3001385
JournalPLoS biology
Volume19
Issue number9
DOIs
StatePublished - Sep 2021

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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