Trophoblast–Macrophage Interactions: a Regulatory Network for the Protection of Pregnancy

Authors

  • Stefan Fest,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA;
    2.  Department of Paediatrics, Experimental Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany;
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  • Paulomi B. Aldo,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA;
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  • V. M. Abrahams,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA;
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  • I. Visintin,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA;
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  • A. Alvero,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA;
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  • R. Chen,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA;
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  • S. L. Chavez,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA;
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  • R. Romero,

    1.  The Perinatology Research Branch, National Institute of Child Health and Human Development, Detroit, MI, USA
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  • G. Mor

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA;
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Gil Mor, Department of Obstetrics, Gynecology, and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, 333 Cedar Street, FMB 301, New Haven, CT 06520, USA.
E-mail: gil.mor@yale.edu

Abstract

Problem  Macrophages are one of the first immune cells observed at the implantation site. Their presence has been explained as the result of an immune response toward paternal antigens. The mechanisms regulating monocyte migration and differentiation at the implantation site are largely unknown. In the present study, we demonstrate that trophoblast cells regulate monocyte migration and differentiation. We propose that trophoblast cells ‘educate’ monocytes/macrophages to create an adequate environment that promote trophoblast survival.

Method of study  CD14+ monocytes were isolated from peripheral blood using magnetic beads. Co-culture experiments were conducted using a two-chamber system. Monocytes were stimulated with lipopolysaccharide (LPS) and cytokine levels were determined using multiplex cytokine detecting assay.

Results  Trophoblast cells increase monocyte migration and induce a significant increase in the secretion and production of the pro-inflammatory cytokines [interleukin-6 (IL-6), IL-8, tumor necrosis factor-α] and chemokines (growth-related oncogen-α, monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, RANTES). Furthermore, the response of monocytes to LPS was different in monocytes pre-exposed to trophoblast cells.

Conclusion  The results of this study suggest that trophoblast cells are able to recruit and successfully educate monocytes to produce and secrete a pro-inflammatory cytokine and chemokine profile supporting its growth and survival. Furthermore we demonstrate that trophoblast cells can modulate monocytes response to bacterial stimuli.

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