IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation
Pietro Presicce, … , Alan H. Jobe, Suhas G. Kallapur
Pietro Presicce, … , Alan H. Jobe, Suhas G. Kallapur
Published March 22, 2018
Citation Information: JCI Insight. 2018;3(6):e98306. https://doi.org/10.1172/jci.insight.98306.
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Research Article Immunology Reproductive biology

IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation

Abstract

Neutrophil infiltration of the chorioamnion-decidua tissue at the maternal-fetal interface (chorioamnionitis) is a leading cause of prematurity, fetal inflammation, and perinatal mortality. We induced chorioamnionitis in preterm rhesus macaques by intraamniotic injection of LPS. Here, we show that, during chorioamnionitis, the amnion upregulated phospho-IRAK1–expressed neutrophil chemoattractants CXCL8 and CSF3 in an IL-1–dependent manner. IL-1R blockade decreased chorio-decidua neutrophil accumulation, neutrophil activation, and IL-6 and prostaglandin E2 concentrations in the amniotic fluid. Neutrophils accumulating in the chorio-decidua had increased survival mediated by BCL2A1, and IL-1R blockade also decreased BCL2A1+ chorio-decidua neutrophils. Readouts for inflammation in a cohort of women with preterm delivery and chorioamnionitis were similar to findings in the rhesus macaques. IL-1 is a potential therapeutic target for chorioamnionitis and associated morbidities.

Authors

Pietro Presicce, Chan-Wook Park, Paranthaman Senthamaraikannan, Sandip Bhattacharyya, Courtney Jackson, Fansheng Kong, Cesar M. Rueda, Emily DeFranco, Lisa A. Miller, David A. Hildeman, Nathan Salomonis, Claire A. Chougnet, Alan H. Jobe, Suhas G. Kallapur

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Figure 1

Close similarities between rhesus intrauterine inflammation and human chorioamnionitis (chorio).

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Close similarities between rhesus intrauterine inflammation and human ch...
Chorio was induced in rhesus macaques by intraamniotic (IA) LPS at 80% gestation with delivery 16 hours later. Samples were collected immediately after birth from women delivering preterm, and chorioamnionitis was diagnosed by placenta histology. (A) Chorio-decidua cells were scraped and digested with protease/DNAase, and single cell suspensions were used for multiparameter flow cytometry phenotyping (rhesus chorio neg., n = 16; rhesus chorio pos., n = 13; human chorio neg., n = 8; human chorio pos., n = 7). Note the close similarities in proportions of CD45+ subsets in rhesus vs. human neutrophil predominance in chorio pos. groups. Data are mean ± SEM, *P < 0.05 between comparators by Mann-Whitney test. (B) Representative fetal membrane (chorioamnion-decidua, CAD; n = 5) H&E histology. Note the neutrophil infiltration at the chorio-decidua interface (white arrowheads) in both rhesus and human chorio (am, amnion; ch, chorion; dp, decidua parietalis). (C) Expression of mRNAs by quantitative PCR (Taqman probes) in the fetal membranes during chorio (rhesus chorio pos., n = 4–10; human chorio pos., n = 4–11). Average mRNA values are fold increases over the average value for control or no chorio (red dashed line) after internally normalizing to the housekeeping 18S RNA. Expression of many genes were similar in the rhesus and humans.