Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque
Pietro Presicce,
Monica Cappelletti,
Marco Morselli,
Feiyang Ma,
Paranthaman Senthamaraikannan,
Giulia Protti,
Brian B. Nadel,
Laila Aryan,
Mansoureh Eghbali,
Lukasz Salwinski,
Neema Pithia,
Emily De Franco,
Lisa A. Miller,
Matteo Pellegrini,
Alan H. Jobe,
Claire A. Chougnet,
Suhas G. Kallapur
Affiliations
Pietro Presicce
Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA
Monica Cappelletti
Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA
Marco Morselli
Department of Molecular, Cell and Developmental Biology Medicine at the University of California Los Angeles, Los Angeles, CA, USA; Institute for Quantitative and Computational Biosciences – Collaboratory at the University of California Los Angeles, Los Angeles, CA, USA
Feiyang Ma
Department of Molecular, Cell and Developmental Biology Medicine at the University of California Los Angeles, Los Angeles, CA, USA; Institute for Quantitative and Computational Biosciences – Collaboratory at the University of California Los Angeles, Los Angeles, CA, USA
Paranthaman Senthamaraikannan
Division of Neonatology/Pulmonary Biology, Cincinnati Children’s Hospital Research Foundation, The University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Immunobiology, Cincinnati Children’s Hospital Research Foundation, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
Giulia Protti
Institute for Quantitative and Computational Biosciences – Collaboratory at the University of California Los Angeles, Los Angeles, CA, USA; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
Brian B. Nadel
Department of Molecular Cellular and Developmental Biology, and Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA, USA; California National Primate Research Center, University of California Davis, Davis, CA, USA
Laila Aryan
Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA
Mansoureh Eghbali
Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA
Lukasz Salwinski
UCLA-DOE Institute of Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA, USA
Neema Pithia
Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA
Emily De Franco
Department of Obstetrics/Gynecology, Maternal-Fetal Medicine, University of Cincinnati, Cincinnati, OH, USA
Lisa A. Miller
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California Davis, CA, USA
Matteo Pellegrini
Department of Molecular, Cell and Developmental Biology Medicine at the University of California Los Angeles, Los Angeles, CA, USA; Institute for Quantitative and Computational Biosciences – Collaboratory at the University of California Los Angeles, Los Angeles, CA, USA
Alan H. Jobe
Division of Neonatology/Pulmonary Biology, Cincinnati Children’s Hospital Research Foundation, The University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Immunobiology, Cincinnati Children’s Hospital Research Foundation, The University of Cincinnati College of Medicine, Cincinnati, OH, USA
Claire A. Chougnet
Division of Immunobiology, Cincinnati Children’s Hospital Research Foundation, and the University of Cincinnati College of Medicine, Cincinnati, OH, USA
Suhas G. Kallapur
Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA; Corresponding author
Summary: Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm Rhesus macaque model of IUI induced by lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (RNA-seq) amnion transcriptomic profiles were remarkably similar in both Rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on nuclear factor κB (NF-κB) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.
