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

• Published in: PLoS biology Vol. 19; no. 9; p. e3001385
• Main Authors: Cappelletti, Monica, Presicce, Pietro, Feiyang, Ma, Senthamaraikannan, Paranthaman, Miller, Lisa A., Pellegrini, Matteo, Sim, Myung S., Jobe, Alan H., Divanovic, Senad, Way, Sing Sing, Chougnet, Claire A., Kallapur, Suhas G.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.09.2021; Public Library of Science (PLoS)
• Subjects: Amnion; Amniotic fluid; Animals; Biology and Life Sciences; Biomarkers; Chemotaxis; Cytokines; Decidua; Disease Models, Animal; E coli; Escherichia coli; Escherichia coli - pathogenicity; Escherichia coli Infections - complications; Escherichia coli Infections - immunology; Female; Fetuses; Flow cytometry; Gene sequencing; Health aspects; Homeostasis; Immune response; Immune system; Immunity; Infections; Infiltration; Inflammation; Interferon; Interleukin 6; Labor; Leukocytes (neutrophilic); Lipopolysaccharides; Lipopolysaccharides - toxicity; Macaca mulatta; Medicine and Health Sciences; Microorganisms; Neutrophils; Observations; Obstetric Labor, Premature - pathology; Pregnancy; Pregnancy Complications - immunology; Prostaglandins; Rhesus monkey; Sepsis; SUMO protein; United States
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3001385

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.