Open AccessThe induction of preterm labor in rhesus macaques is determined by the strength of immune response to intrauterine infection
Author(s) -
Monica Cappelletti,
Pietro Presicce,
Feiyang Ma,
Paranthaman Senthamaraikannan,
Lisa Miller,
Matteo Pellegrini,
Myung Shin Sim,
Alan H. Jobe,
Senad Divanovic,
Sing Sing Way,
Claire Chougnet,
Suhas G. Kallapur
Publication year - 2021
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001385
Subject(s) - biology , immune system , inflammation , immunology , lipopolysaccharide , rhesus macaque , escherichia coli , innate immune system , infiltration (hvac) , chorioamnionitis , amnion , microbiology and biotechnology , fetus , pregnancy , gene , physics , genetics , thermodynamics , biochemistry
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.