Author:
Sun Xinyue,Xie Hongbing,Zhang Haixia,Li Zhidan,Qi Houbao,Yang Chunyan,Liu Xianbing,Ren Liqin,Jiang Yuzhu,Hu Xuemei
Abstract
Abstract
Background
Primary infection of Toxoplasma gondii can cause serious abnormal pregnancy outcomes such as miscarriage and stillbirth. Inhibitory molecule B7-H4 is abundantly expressed in dendritic cells (DCs) and plays an important role in maintaining immune tolerance. However, the role of B7-H4 in decidual DCs (dDCs) in T. gondii-induced abnormal pregnancy outcomes is not clear.
Methods
We established T. gondii-infected abnormal pregnancy model in wild-type (WT) and B7-H4 knockout (B7-H4−/−) pregnant mice in vivo and cultured primary human dDCs in vitro. The abnormal pregnancy outcomes were observed and the expression of B7-H4, functional molecules (CD80, CD86, and MHC-II or HLA-DR), indoleamine 2,3-dioxygenase (IDO), cytokines (IL-10 and IL-12), and signaling molecules JAK2/STAT3 in dDCs was detected by flow cytometry and Western blot.
Results
Our results showed that T. gondii infection significantly decreased B7-H4 expression in dDCs. In addition, B7-H4−/− infected pregnant mice showed much more severe abnormal pregnancy outcomes than their counterparts. Importantly, B7-H4−/− infection further regulated the expression of molecules (CD80, CD86, and MHC-II or HLA-DR), enzyme IDO, and cytokines (IL-10 and IL-12) in dDCs. We further discovered that B7-H4−/− infection impairs the JAK2/STAT3 pathway, contributing to dDC dysfunction.
Conclusions
Taken together, the results show that reduction of B7-H4 by T. gondii infection significantly modulates the decrease in cytokine IL-10 and enzyme IDO and the increase in cytokine IL-12, contributing to dDC dysfunction. Moreover, the JAK2/STAT3 pathway is involved in the regulation of B7-H4 by T. gondii infection and in the subsequent IDO and cytokine production, which ultimately contributes to abnormal pregnancy outcomes.
Graphical Abstract
Funder
the National Natural Science Foundation of China
National Natural Science Foundation of China
Taishan Scholar Foundation of Shandong province
Publisher
Springer Science and Business Media LLC
Subject
Infectious Diseases,Parasitology
Cited by
6 articles.
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