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 4

IA LPS induced chorio-decidua neutrophil cytokine production, and activation is IL-1 dependent.

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IA LPS induced chorio-decidua neutrophil cytokine production, and activa...
(A) Expression of TNF-α in chorio-decidua neutrophils was assessed by flow cytometry. rhIL-1ra significantly decreased the frequency of TNF-α+ chorio-decidua neutrophils (Ctrl, n = 13; LPS, n = 12; LPS + rhIL-1ra, n = 6). (B–E) Chorioamnion-decidua sections from paraffin-embedded blocks were stained with DAPI (blue), IL-8/CXCL8 (red), and neutrophil elastase (green). Representative sections (n = 4) are shown from the animal groups: control (B), IA LPS (C), and LPS + rhIL-1ra (D). In magnified images in the inserts in C and D show cells with polymorphonuclear neutrophil morphology coexpressing IL-8/CXCL8 and neutrophil elastase. (E) Cell count/high-powered field (HPF, 40×) of IL-8/CXCL8+ neutrophils in the chorioamnion-decidua interface (Ctrl, n = 4; LPS, n = 4; LPS + rhIL-1ra, n = 4). (F and G) Expression of activation molecules in chorio-decidua neutrophils was assessed by flow cytometry (Ctrl, n = 7; LPS, n = 7; LPS + rhIL-1ra, n = 3). rhIL-1ra decreased LPS-induced expression of CD16 nonsignificantly (F) and CD63 significantly (G) in chorio-decidua neutrophils. (H) Positive correlation of CD63 expression and TNF-α in neutrophils from LPS-exposed animals (n = 6; r2 = 0.69; P = 0.03). am, amnion; ch, chorion; dp, decidua parietalis. Data are mean ± SEM, *P < 0.05 between comparators by Mann-Whitney test.