title: Chinese 1 strain of Toxoplasma gondii excreted-secreted antigens negatively modulate Foxp3 via inhibition of the TGFßRII/Smad2/Smad3/Smad4 pathway.
abstract: Toxoplasma gondii is an opportunistic intracellular parasite and is considered an important aetiological factor in the process of abortion, especially as occurs in early gestation. Chinese 1 strain of T. gondii is a dominant genotype prevalent in China. Although it is known that early foetal resorption triggered by RH strain of T. gondii is attributable to immune mechanisms rather than its direct effect in uterus, the underlying mechanism of the abortion caused by Chinese 1 strain remains unclear. This study was designed to investigate the effect of excreted-secreted antigens (ESA) of Chinese 1 strain of T. gondii on the expression of forkhead box transcription factor (Foxp3) as it pertains to early pregnancy and abortion. ESA caused a marked inhibition in the expression of Foxp3 both in vivo and in vitro. In addition, ESA negatively modulated Smad2 and Smad3 at the posttranslational level. Smad2 siRNA cooperated with ESA to further suppress the level of Foxp3. This inhibitory effect on Foxp3 expression was partially abrogated by overexpression of Smad2, Smad3 and Smad4. Additionally, ESA attenuated the expression of TGFßRII, whereas TGFßRII agonist could profoundly reversed the decreased Foxp3 triggered by ESA. Collectively, the findings suggested that ESA restricted Foxp3 expression by inhibiting TGFßRII/Smad2/Smad3/Smad4 signalling, ultimately resulting in abortion.
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
authors.forename: Caiqun
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Shen
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
authors.forename: Yinong
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
authors.forename: Chunzhao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
authors.forename: Liting
authors.initials: L
authors.lastname: Wu
mesh_terms: D000028:Abortion, Induced; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000953:Antigens, Protozoan / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D051379:Mice; D015735:Mifepristone; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D014122:Toxoplasma / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000953:Antigens, Protozoan; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D015735:Mifepristone; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Chinese 1 strain of Toxoplasma gondii; Foxp3; TGFßRII/Smad2/Smad3/Smad4; excreted-secreted antigens