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

Autor: Xinyue Sun, Hongbing Xie, Haixia Zhang, Zhidan Li, Houbao Qi, Chunyan Yang, Xianbing Liu, Liqin Ren, Yuzhu Jiang, Xuemei Hu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Parasites & Vectors, Vol 15, Iss 1, Pp 1-17 (2022)
Druh dokumentu: article
ISSN: 1756-3305
DOI: 10.1186/s13071-022-05263-1
Popis: 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
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