Amniotic fluid neutrophils can phagocytize bacteria: A mechanism for microbial killing in the amniotic cavity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138926/1/aji12723_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138926/2/aji12723.pd

Inflammasome assembly in the chorioamniotic membranes during spontaneous labor at term

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137494/1/aji12648.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137494/2/aji12648_am.pd

Inflammasome activation during spontaneous preterm labor with intraâ amniotic infection or sterile intraâ amniotic inflammation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146295/1/aji13049.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146295/2/aji13049_am.pd

Are B cells altered in the decidua of women with preterm or term labor?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149277/1/aji13102_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149277/2/aji13102.pd

The immunophenotype of amniotic fluid leukocytes in normal and complicated pregnancies

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142907/1/aji12827.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142907/2/aji12827_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142907/3/aji12827-sup-0001-FigS1.pd

RNA Sequencing Reveals Diverse Functions of Amniotic Fluid Neutrophils and Monocytes/Macrophages in Intra-Amniotic Infection

Intra-amniotic infection, the invasion of microbes into the amniotic cavity resulting in inflammation, is a clinical condition that can lead to adverse pregnancy outcomes for the mother and fetus as well as severe long-term neonatal morbidities. Despite much research focused on the consequences of intra-amniotic infection, there remains little knowledge about the innate immune cells that respond to invading microbes. We performed RNA-seq of sorted amniotic fluid neutrophils and monocytes/macrophages from women with intra-amniotic infection to determine the transcriptomic differences between these innate immune cells. Further, we sought to identify specific transcriptomic pathways that were significantly altered by the maternal or fetal origin of amniotic fluid neutrophils and monocytes/macrophages, the presence of a severe fetal inflammatory response, and pregnancy outcome (i.e., preterm or term delivery). We show that significant transcriptomic differences exist between amniotic fluid neutrophils and monocytes/macrophages from women with intra-amniotic infection, indicating the distinct roles these cells play. The transcriptome of amniotic fluid immune cells varies based on their maternal or fetal origin, and the significant transcriptomic differences between fetal and maternal monocytes/macrophages imply that those of fetal origin exhibit impaired functions. Notably, transcriptomic changes in amniotic fluid monocytes/macrophages suggest that these immune cells collaborate with neutrophils in the trafficking of fetal leukocytes throughout the umbilical cord (i.e., funisitis). Finally, amniotic fluid neutrophils and monocytes/macrophages from preterm deliveries display enhanced transcriptional activity compared to those from term deliveries, highlighting the protective role of these cells during this vulnerable period. Collectively, these findings demonstrate the underlying complexity of local innate immune responses in women with intra-amniotic infection and provide new insights into the functions of neutrophils and monocytes/macrophages in the amniotic cavity. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements

Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Inflammation is causally linked to preterm birth; therefore, finding an intervention that dampens maternal and fetal inflammatory responses may provide a new strategy to prevent adverse pregnancy and neonatal outcomes. Using animal models of systemic maternal inflammation [intraperitoneal injection of lipopolysaccharide (LPS)] and fetal inflammation (intra-amniotic administration of LPS), we found that (1) systemic inflammation induced adverse pregnancy and neonatal outcomes by causing a severe maternal cytokine storm and a mild fetal cytokine response; (2) fetal inflammation induced adverse pregnancy and neonatal outcomes by causing a mild maternal cytokine response and a severe fetal cytokine storm; (3) exendin-4 (Ex4) treatment of dams with systemic inflammation or fetal inflammation improved adverse pregnancy outcomes by modestly reducing the rate of preterm birth; (4) Ex4 treatment of dams with systemic, but not local, inflammation considerably improved neonatal outcomes, and such neonates continued to thrive; (5) systemic inflammation facilitated the diffusion of Ex4 through the uterus and the maternal–fetal interface; (6) neonates born to Ex4-treated dams with systemic inflammation displayed a similar cytokine profile to healthy control neonates; and (7) treatment with Ex4 had immunomodulatory effects by inducing an M2 macrophage polarization and increasing anti-inflammatory neutrophils, as well as suppressing the expansion of CD8+ regulatory T cells, in neonates born to dams with systemic inflammation. Collectively, these results provide evidence that dampening maternal systemic inflammation through novel interventions, such as Ex4, can improve the quality of life for neonates born to women with this clinical condition

Neutrophil extracellular traps in acute chorioamnionitis: AÂ mechanism of host defense

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136301/1/aji12617_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136301/2/aji12617.pd