B7-H4 reduction induced by Toxoplasma gondii infection results in dysfunction of decidual dendritic cells by regulating the JAK2/STAT3 pathway

• Published in: Parasites & vectors 2022-05, Vol.15 (1), p.157-157, Article 157
• Main Authors: Sun, Xinyue, Xie, Hongbing, Zhang, Haixia, Li, Zhidan, Qi, Houbao, Yang, Chunyan, Liu, Xianbing, Ren, Liqin, Jiang, Yuzhu, Hu, Xuemei
• Format: Article
• Language: English
• Subjects: Abnormal pregnancy; Animals; Antigens; B7-1 Antigen - genetics; B7-H4; CD80 antigen; CD86 antigen; Complications and side effects; Cytokines; Decidua; Decidual DCs; Dendritic Cells; Enzymes; Female; Females; Fetuses; Flow cytometry; Genetic aspects; Health aspects; Histocompatibility antigen HLA; Immunological tolerance; Infections; Inhibitory molecule; Interleukin 10; Interleukin 12; Janus kinase 2; Laboratory animals; Major histocompatibility complex; Maternal & child health; Maternal–fetal tolerance; Mice; Patient outcomes; Penicillin; Physiological aspects; Pregnancy; Pregnancy Complications, Infectious - immunology; Pregnancy Complications, Infectious - pathology; Reduction; Stat3 protein; Toxoplasma; Toxoplasma gondii; Toxoplasmosis; Toxoplasmosis - immunology; Toxoplasmosis - metabolism; Tryptophan 2,3-dioxygenase; V-Set Domain-Containing T-Cell Activation Inhibitor 1 - metabolism
• ISSN: 1756-3305; 1756-3305
• DOI: 10.1186/s13071-022-05263-1

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. 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. 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. 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.