Toxoplasma gondii Infection Regulates the Balance of Activating and Inhibitory Receptors on Decidual Natural Killer Cells

Yuzhu Jiang,Haixia Zhang,Markus M. Heimesaat,Mingdong Zhao,Xiaoyan Xu,Xianbing Liu,Ling Zhang,Xiaoyu Zhai,Xuemei Hu

doi:10.1371/journal.pone.0055432

Yuzhu Jiang, Haixia Zhang + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0055432

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Journal: PLoS ONE	Publication Date: Feb 5, 2013
Citations: 17	License type: CC BY 4.0

Affiliation: Binzhou University, Binzhou Medical University

Abstract

Inhibitory receptors and activating receptor expressed on decidual natural killer (dNK) cells are generally believed to be important in abnormal pregnancy outcomes and induced adverse pregnancy. However, if Toxoplasma gondii (T. gondii) infection induced abnormal pregnancy was related to dNK cells changes is not clear. In this study, we used human dNK cells co-cultured with human extravillous cytotrophoblast (EVT) cells following YFP-Toxoplasma gondii (YFP-T. gondii) infection in vitro and established animal pregnant infection model. Levels of inhibitory receptors KIR2DL4 and ILT-2, their ligand HLA-G, and activating receptor NKG2D in human decidua, and NKG2A and its ligand Qa-1 and NKG2D in mice uterine were analyzed by real-time PCR and flow cytometry with levels of NKG2D significantly higher than those of KIR2DL4 and ILT-2 in vitro and in invo. The level of NKG2D was positively correlated with cytotoxic activity of dNK cells in vitro. Numbers of abnormal pregnancies were significantly greater in the infected group than in the control group. This result demonstrated that the increased NKG2D expression and imbalance between inhibitory receptors of dNK cells and HLA-G may contribute to abnormal pregnancy outcomes observed upon maternal infection with T. gondii.

Highlights

Toxoplasma gondii is a widespread obligate intracellular protozoan parasite that can infect all warm-blooded animals including humans and mice [1]
The levels of mRNAs encoding inhibitory receptors KIR2DL4 and ILT-2, of activating receptor NKG2D, and of ligand HLA-G were measured by real-time PCR (Fig. 2)
The levels of inhibitory receptors KIR2DL4 and ILT-2, and their ligand HLA-G and activating receptor NKG2D were measured by flow cytometry (Table 2)

Summary

Introduction

Toxoplasma gondii is a widespread obligate intracellular protozoan parasite that can infect all warm-blooded animals including humans and mice [1]. T. gondii infection may result in maternal immune deregulation and can cause a variety of syndromes during pregnancy, when infection occurs during the first trimester, such as miscarriage, spontaneous abortion, or fetal teratogenesis [2]. More than 70% of lymphocytes in the decidua in early pregnancy are natural killer cells. These cells are tolerant to fetal trophoblastic cells, even though NK cells are innate immune effectors, able to exert a prompt cytolytic activity on virally infected or cancerous cells without prior stimulation [4]. Disturbance of maternal NK immune tolerance to the fetus may result in the high incidence of abnormal pregnancies observed in mothers infected with T. gondii

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