TNF-Signaling Modulates Neutrophil-Mediated Immunity at the Feto-Maternal Interface During LPS-Induced Intrauterine Inflammation

Frontiers in Immunology

卷:11

Lisa A. Miller²  Feiyang Ma³  Courtney M. Jackson⁴  Shibabrata Mukherjee⁴  Claire A. Chougnet⁴  Alan H. Jobe⁵  Paranthaman Senthamaraikannan⁵  Suhas G. Kallapur⁶  Pietro Presicce⁶  Monica Cappelletti⁶  Marco Morselli⁷  Matteo Pellegrini⁷ 

[1] California National Primate Research Center, University of California, Davis, Davis, CA, United States;

[2] Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States;

[3] Department of Molecular, Cell and Developmental Biology Medicine, University of California, Los Angeles, Los Angeles, CA, United States;

[4] Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, The University of Cincinnati College of Medicine, Cincinnati, OH, United States;

[5] Division of Neonatology/Pulmonary Biology, Cincinnati Children's Hospital Research Foundation, The University of Cincinnati College of Medicine, Cincinnati, OH, United States;

[6] Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States;

[7] Institute for Quantitative and Computational Biosciences–Collaboratory, University of California, Los Angeles, Los Angeles, CA, United States;

关键词: chorioamnionitis;    neutrophils;    inflammation;    innate immunity;    reproductive immunology;   

DOI  :  10.3389/fimmu.2020.00558

来源: DOAJ

【 摘 要 】

Accumulation of activated neutrophils at the feto-maternal interface is a defining hallmark of intrauterine inflammation (IUI) that might trigger an excessive immune response during pregnancy. Mechanisms responsible of this massive neutrophil recruitment are poorly investigated. We have previously showed that intraamniotic injection of LPS in rhesus macaques induced a neutrophil predominant inflammatory response similar to that seen in human IUI. Here, we demonstrate that anti-TNF antibody (Adalimumab) inhibited ~80% of genes induced by LPS involved in inflammatory signaling and innate immunity in chorio-decidua neutrophils. Consistent with the gene expression data, TNF-blockade decreased LPS-induced neutrophil accumulation and activation at the feto-maternal interface. We also observed a reduction in IL-6 and other pro-inflammatory cytokines but not prostaglandins concentrations in the amniotic fluid. Moreover, TNF-blockade decreased mRNA expression of inflammatory cytokines in the chorio-decidua but not in the uterus, suggesting that inhibition of TNF-signaling decreased the inflammation in a tissue-specific manner within the uterine compartment. Taken together, our results demonstrate a predominant role for TNF-signaling in modulating the neutrophilic infiltration at the feto-maternal interface during IUI and suggest that blockade of TNF-signaling could be considered as a therapeutic approach for IUI, the major leading cause of preterm birth.

【 授权许可】

Unknown