Trophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages

Authors

  • Paulomi B. Aldo,

    1. Department of Obstetrics Gynecology and Reproductive Science, Yale University School of Medicine, New Haven, CT, USA
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  • Karen Racicot,

    1. Department of Obstetrics Gynecology and Reproductive Science, Yale University School of Medicine, New Haven, CT, USA
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  • Vinicius Craviero,

    1. Department of Obstetrics Gynecology and Reproductive Science, Yale University School of Medicine, New Haven, CT, USA
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  • Seth Guller,

    1. Department of Obstetrics Gynecology and Reproductive Science, Yale University School of Medicine, New Haven, CT, USA
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  • Roberto Romero,

    1. Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS, Detroit, MI, USA
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  • Gil Mor

    Corresponding author
    1. Department of Obstetrics Gynecology and Reproductive Science, Yale University School of Medicine, New Haven, CT, USA
    • Correspondence

      Gil Mor, MD, PhD, Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Reproductive Sciences, Yale University School of Medicine, 333 Cedar St., LSOG 305A, New Haven, CT 06520, USA.

      E-mail: gil.mor@yale.edu

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Abstract

Problem

During early pregnancy, macrophages and trophoblast come into close contact during placenta development, and regulated cross talk between these cellular compartments is crucial for maintaining a healthy pregnancy. As trophoblast cells constitutively secrete many chemokines and cytokines, we hypothesize that trophoblast-secreted factors can differentiate monocytes into a decidual phenotype. In this study, we describe a unique macrophage phenotype, following monocytes’ exposure to trophoblast-soluble factors.

Method of study

Peripheral blood monocytes were treated with or without conditioned media (CM) from first trimester trophoblast cells. Phenotypic changes and phagocytic capacity were determined by flow cytometry. Cytokine and chemokine production was determined by multiplex analysis.

Results

Monocytes exposed to trophoblast factors undergo morphologic changes characterized by a gain in size and complexity and acquire a unique phenotype characterized by gain of CD14 surface expression as well as CD16. The presence of CD14+/CD16+ macrophages was confirmed in normal decidua. These cells secrete higher levels of IL-1b, IL-10, and IP-10 and have increased capacity for phagocytosis.

Conclusion

We demonstrate that trophoblast-secreted factors can induce monocyte differentiation into a unique macrophage phenotype. These findings suggest that the microenvironment of the placenta can modulate the phenotype of macrophages present at the decidua.

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