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

• DOI: 10.1172/jci.insight.98306
• Publication Date: 2018-03-21T15:01:17Z
• Authors: Pietro Presicce; Chan-Wook Park; Paranthaman Senth...; 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
• Keywords: Lipopolysaccharides; 0301 basic medicine; Neutrophils; Immunology; Apoptosis; Reproductive health and childbirth; Low Birth Weight and Health of the Newborn; Minor Histocompatibility Antigens; 03 medical and health sciences; Preterm; Pregnancy; Receptors; Infant Mortality; Decidua; Animals; Humans; Amnion; Pediatric; Inflammation; Reproductive Biology; 0303 health sciences; Interleukin-8; Infant, Newborn; Infant; Chorion; Perinatal Period - Conditions Originating in Perinatal Period; Newborn; Macaca mulatta; 3. Good health; Infectious Diseases; Good Health and Well Being; Chorioamnionitis; Interleukin-1 Receptor-Associated Kinases; Proto-Oncogene Proteins c-bcl-2; Neutrophil Infiltration; Cytokines; Female; Signal Transduction; Interleukin-1

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.