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Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines.

Publication ,  Journal Article
Ander, SE; Rudzki, EN; Arora, N; Sadovsky, Y; Coyne, CB; Boyle, JP
Published in: mBio
January 9, 2018

Toxoplasma gondii is a major source of congenital disease worldwide, but the cellular and molecular factors associated with its vertical transmission are largely unknown. In humans, the placenta forms the key interface between the maternal and fetal compartments and forms the primary barrier that restricts the hematogenous spread of microorganisms. Here, we utilized primary human trophoblast (PHT) cells isolated from full-term placentas and human midgestation chorionic villous explants to determine the mechanisms by which human trophoblasts restrict and respond to T. gondii infection. We show that placental syncytiotrophoblasts, multinucleated cells that are in direct contact with maternal blood, restrict T. gondii infection at two distinct stages of the parasite lytic cycle-at the time of attachment and also during intracellular replication. Utilizing comparative transcriptome sequencing (RNA-seq) transcriptional profiling, we also show that human placental trophoblasts from both the second and third trimesters respond uniquely to T. gondii infection compared to trophoblast cell lines, typified by the upregulation of several immunity-related genes. One of the most differentially induced genes was the chemokine CCL22, which relies on the secretion of a parasite effector(s) either during or after invasion for its induction. Collectively, our findings provide new insights into the mechanisms by which the human placenta restricts the vertical transmission of T. gondii at early and late stages of human pregnancy and demonstrate the existence of at least two interferon-independent pathways that restrict T. gondii access to the fetal compartment.IMPORTANCEToxoplasma gondii is a major source of congenital disease worldwide and must breach the placental barrier to be transmitted from maternal blood to the developing fetus. The events associated with the vertical transmission of T. gondii are largely unknown. Here, we show that primary human syncytiotrophoblasts, the fetus-derived cells that comprise the primary placental barrier, restrict T. gondii infection at two distinct stages of the parasite life cycle and respond to infection by inducing a unique immunomodulatory transcriptional profile. Collectively, our findings provide important insights into the mechanisms by which human syncytiotrophoblasts restrict T. gondii infection at early and late stages of human pregnancy, identify both permissive and resistant human placental cell types, and identify the placenta-enriched signaling pathways induced in response to infection.

Duke Scholars

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Published In

mBio

DOI

EISSN

2150-7511

Publication Date

January 9, 2018

Volume

9

Issue

1

Location

United States

Related Subject Headings

  • Trophoblasts
  • Toxoplasma
  • Pregnancy
  • Placenta
  • Organ Culture Techniques
  • Humans
  • Gene Expression Profiling
  • Female
  • Chemokines
  • Cells, Cultured
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ander, S. E., Rudzki, E. N., Arora, N., Sadovsky, Y., Coyne, C. B., & Boyle, J. P. (2018). Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines. MBio, 9(1). https://doi.org/10.1128/mBio.01678-17
Ander, Stephanie E., Elizabeth N. Rudzki, Nitin Arora, Yoel Sadovsky, Carolyn B. Coyne, and Jon P. Boyle. “Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines.MBio 9, no. 1 (January 9, 2018). https://doi.org/10.1128/mBio.01678-17.

Published In

mBio

DOI

EISSN

2150-7511

Publication Date

January 9, 2018

Volume

9

Issue

1

Location

United States

Related Subject Headings

  • Trophoblasts
  • Toxoplasma
  • Pregnancy
  • Placenta
  • Organ Culture Techniques
  • Humans
  • Gene Expression Profiling
  • Female
  • Chemokines
  • Cells, Cultured