Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque

• Published in: iScience Vol. 26; no. 11; p. 108118
• Main Authors: Presicce, Pietro, Cappelletti, Monica, Morselli, Marco, Ma, Feiyang, Senthamaraikannan, Paranthaman, Protti, Giulia, Nadel, Brian B., Aryan, Laila, Eghbali, Mansoureh, Salwinski, Lukasz, Pithia, Neema, De Franco, Emily, Miller, Lisa A., Pellegrini, Matteo, Jobe, Alan H., Chougnet, Claire A., Kallapur, Suhas G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-11-2023; Elsevier
• Subjects: Bioinformatics; Immunology; Omics; Bioinformatics; Immunology; Omics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.108118

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.
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•Amnion participates in host-immune response to IUI via NF-κB activation•NF-κB activation in the amnion is TNF dependent•During IUI, AMCs get activated to express myeloid and innate immune genes
Immunology; Bioinformatics; Omics