LILRB4 Decrease on uDCs Exacerbate Abnormal Pregnancy Outcomes Following Toxoplasma gondii Infection.

Shaowei Zhan,Shaowei Zhan,Haixia Zhang,Haixia Zhang,Chunyan Yang,Chunyan Yang,Xianbing Liu,Xianbing Liu,Liqin Ren,Yuzhu Jiang,Yuzhu Jiang,Zhiqiang Liu,Zhiqiang Liu,Xuemei Hu,Xuemei Hu,Jing Zheng,Mingdong Zhao

doi:10.3389/fmicb.2018.00588

Shaowei Zhan, Shaowei Zhan + Show 15 more

Open Access

https://doi.org/10.3389/fmicb.2018.00588

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Abstract

Toxoplasma gondii (T. gondii) infection in early pregnancy can result in miscarriage, dead fetus, and other abnormalities. The LILRB4 is a central inhibitory receptor in uterine dendritic cells (uDCs) that plays essential immune-regulatory roles at the maternal–fetal interface. In this study, T. gondii-infected human primary uDCs and T. gondii-infected LILRB4-/- pregnant mice were utilized. The immune mechanisms underlying the role of LILRB4 on uDCs were explored in the development of abnormal pregnancy outcomes following T. gondii infection in vitro and in vivo. Our results showed that the expression levels of LILRB4 on uDCs from normal pregnant mice were obviously higher than non-pregnant mice, and peaked in mid-gestation. The LILRB4 expression on uDC subsets, especially tolerogenic subsets, from mid-gestation was obviously down-regulated after T. gondii infection and LILRB4 decrease could further regulate the expression of functional molecules (CD80, CD86, and HLA-DR or MHC II) on uDCs, contributing to abnormal pregnancy outcomes. Our results will shed light on the molecular immune mechanisms of uDCs in abnormal pregnancy outcomes by T. gondii infection.

Highlights

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite capable of infecting a wide range of mammalian hosts including humans
The results showed that CD80, CD86, and HLA-DR in human myeloid DC type 1 (MDC1), myeloid DC type 2 (MDC2), and plasmacytoid DC (PDC) were significantly upregulated after T. gondii infection followed LILRB4 decrease
The results showed that functional molecules CD80, CD86, and HLA-DR expression in LILRB4neutralized infected human MDC1, MDC2, and PDC subsets were further up-regulated compared with the infected uterine dendritic cells (uDCs) subsets

Summary

Introduction

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite capable of infecting a wide range of mammalian hosts including humans. The microenvironment at the maternal–fetal interface plays an important role in maintaining normal pregnancy (Hunt and Robertson, 1996). Multiple immune cells and cytokines at the maternal–fetal interface participate in protecting the semi-allogeneic embryo from maternal attack and promote immune tolerance during pregnancy (Guleria and Sayegh, 2007). Among these immunocompetent cells at the maternal–fetal interface, antigen-presenting cells (APCs) are LILRB4 in T. gondii-Infected Abnormal Pregnancy regarded as important participants in immune regulation during pregnancy (Della Bella et al, 2011)

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