Jose Galaz1,2,3, Roberto Romero1,4,5,6,7,8, Yi Xu1,2, Derek Miller1,2, Rebecca Slutsky1, Dustyn Levenson1,2, Chaur-Dong Hsu1,2,9, Nardhy Gomez-Lopez10,11,12. 1. Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Detroit, MI, USA. 2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA. 3. Department of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. 4. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, United States. 5. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA. 6. Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA. 7. Detroit Medical Center, Detroit, MI, USA. 8. Department of Obstetrics and Gynecology, Florida International University, Miami, FL, USA. 9. Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA. 10. Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Detroit, MI, USA. nardhy.gomez-lopez@wayne.edu. 11. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA. nardhy.gomez-lopez@wayne.edu. 12. Department of Immunology, Microbiology and Biochemistry, Wayne State University School of Medicine, Detroit, MI, USA. nardhy.gomez-lopez@wayne.edu.
Abstract
OBJECTIVE: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Some preterm births are associated with clinical chorioamnionitis; yet, this condition has been poorly investigated. Herein, we characterized the amniotic fluid cellular immune responses in women with preterm clinical chorioamnionitis. METHODS AND SUBJECTS: Amniotic fluid samples were obtained from women with preterm clinical chorioamnionitis and a positive or negative microbiological culture (n = 17). The cellular composition of amniotic fluid was evaluated using fluorescence microscopy, scanning and transmission electron microscopy, and flow cytometry. Women without preterm clinical chorioamnionitis were also examined (n = 10). RESULTS: Amniotic fluid from women with preterm clinical chorioamnionitis and a positive culture had: (1) abundant neutrophils associated with viable and non-viable bacteria, (2) neutrophils performing phagocytosis, (3) neutrophils forming NETs, (4) increased numbers of neutrophils, monocytes/macrophages, and CD4+ T cells, and (5) high expression of IL-1β by neutrophils and monocytes/macrophages. Amniotic fluid from women with preterm clinical chorioamnionitis and proven infection tended to have fewer monocytes/macrophages and CD4+ T cells compared to those without chorioamnionitis. CONCLUSION: We provide the first morphologic and phenotypic characterization of the cellular immune responses in the amniotic cavity of women with preterm clinical chorioamnionitis, a condition associated with adverse neonatal outcomes.
OBJECTIVE: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Some preterm births are associated with clinical chorioamnionitis; yet, this condition has been poorly investigated. Herein, we characterized the amniotic fluid cellular immune responses in women with preterm clinical chorioamnionitis. METHODS AND SUBJECTS: Amniotic fluid samples were obtained from women with preterm clinical chorioamnionitis and a positive or negative microbiological culture (n = 17). The cellular composition of amniotic fluid was evaluated using fluorescence microscopy, scanning and transmission electron microscopy, and flow cytometry. Women without preterm clinical chorioamnionitis were also examined (n = 10). RESULTS: Amniotic fluid from women with preterm clinical chorioamnionitis and a positive culture had: (1) abundant neutrophils associated with viable and non-viable bacteria, (2) neutrophils performing phagocytosis, (3) neutrophils forming NETs, (4) increased numbers of neutrophils, monocytes/macrophages, and CD4+ T cells, and (5) high expression of IL-1β by neutrophils and monocytes/macrophages. Amniotic fluid from women with preterm clinical chorioamnionitis and proven infection tended to have fewer monocytes/macrophages and CD4+ T cells compared to those without chorioamnionitis. CONCLUSION: We provide the first morphologic and phenotypic characterization of the cellular immune responses in the amniotic cavity of women with preterm clinical chorioamnionitis, a condition associated with adverse neonatal outcomes.
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