Chinese 1 Strain of Toxoplasma Gondii Excreted-secreted Antigens Negatively Modulate Foxp3 Via Inhibition of the TGFßRII/Smad2/Smad3/Smad4 Pathway

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2017 Mar 17

PMID 28300338

Citations 7

Authors

Jinling Chen

Caiqun Huang

Dandan Zhu

Pei Shen

Yinong Duan

Jianxin Wang

Chunzhao Yang

Liting Wu

Affiliations

Soon will be listed here.

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.

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References

Hernandez-Cortazar I, Acosta-Viana K, Ortega-Pacheco A, Guzman-Marin E, Aguilar-Caballero A, Jimenez-Coello M . Toxoplasmosis in Mexico: epidemiological situation in humans and animals. Rev Inst Med Trop Sao Paulo. 2015; 57(2):93-103. PMC: 4435006. DOI: 10.1590/S0036-46652015000200001. View

Edwards J, Dubey J . Toxoplasma gondii abortion storm in sheep on a Texas farm and isolation of mouse virulent atypical genotype T. gondii from an aborted lamb from a chronically infected ewe. Vet Parasitol. 2012; 192(1-3):129-36. DOI: 10.1016/j.vetpar.2012.09.037. View

Lin W, Haribhai D, Relland L, Truong N, Carlson M, Williams C . Regulatory T cell development in the absence of functional Foxp3. Nat Immunol. 2007; 8(4):359-68. DOI: 10.1038/ni1445. View

Jasper M, Tremellen K, Robertson S . Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Mol Hum Reprod. 2006; 12(5):301-8. DOI: 10.1093/molehr/gal032. View

Duan Y, Gu X, Zhu D, Sun W, Chen J, Feng J . Schistosoma japonicum soluble egg antigens induce apoptosis and inhibit activation of hepatic stellate cells: a possible molecular mechanism. Int J Parasitol. 2014; 44(3-4):217-24. DOI: 10.1016/j.ijpara.2013.11.003. View

Lu L, Ma J, Li Z, Lan Q, Chen M, Liu Y . All-trans retinoic acid promotes TGF-β-induced Tregs via histone modification but not DNA demethylation on Foxp3 gene locus. PLoS One. 2011; 6(9):e24590. PMC: 3172235. DOI: 10.1371/journal.pone.0024590. View

Zhou P, Chen Z, Li H, Zheng H, He S, Lin R . Toxoplasma gondii infection in humans in China. Parasit Vectors. 2011; 4:165. PMC: 3174123. DOI: 10.1186/1756-3305-4-165. View

Jana S, Jailwala P, Haribhai D, Waukau J, Glisic S, Grossman W . The role of NF-kappaB and Smad3 in TGF-beta-mediated Foxp3 expression. Eur J Immunol. 2009; 39(9):2571-83. DOI: 10.1002/eji.200939201. View

Shiono Y, Mun H, He N, Nakazaki Y, Fang H, Furuya M . Maternal-fetal transmission of Toxoplasma gondii in interferon-gamma deficient pregnant mice. Parasitol Int. 2007; 56(2):141-8. DOI: 10.1016/j.parint.2007.01.008. View

10.

Park S, Cho H, Jeong Y, Shin J, Kang J, Park K . Melittin inhibits TGF-β-induced pro-fibrotic gene expression through the suppression of the TGFβRII-Smad, ERK1/2 and JNK-mediated signaling pathway. Am J Chin Med. 2014; 42(5):1139-52. DOI: 10.1142/S0192415X14500712. View

11.

Cheng W, Liu F, Li M, Hu X, Chen H, Pappoe F . Variation detection based on next-generation sequencing of type Chinese 1 strains of Toxoplasma gondii with different virulence from China. BMC Genomics. 2015; 16:888. PMC: 4628340. DOI: 10.1186/s12864-015-2106-z. View

12.

Hahn J, Falck V, Jirik F . Smad4 deficiency in T cells leads to the Th17-associated development of premalignant gastroduodenal lesions in mice. J Clin Invest. 2011; 121(10):4030-42. PMC: 3195457. DOI: 10.1172/JCI45114. View

13.

Hori S, Sakaguchi S . Foxp3: a critical regulator of the development and function of regulatory T cells. Microbes Infect. 2004; 6(8):745-51. DOI: 10.1016/j.micinf.2004.02.020. View

14.

Tang C, Lei J, Wang T, Lu S, Guan F, Liu W . Effect of CD4+ CD25+ regulatory T cells on the immune evasion of Schistosoma japonicum. Parasitol Res. 2010; 108(2):477-80. DOI: 10.1007/s00436-010-2089-2. View

15.

Xiao S, Jin H, Korn T, Liu S, Oukka M, Lim B . Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression. J Immunol. 2008; 181(4):2277-84. PMC: 2722959. DOI: 10.4049/jimmunol.181.4.2277. View

16.

Cesbron-Delauw M, Capron A . Excreted/secreted antigens of Toxoplasma gondii--their origin and role in the host-parasite interaction. Res Immunol. 1993; 144(1):41-4. DOI: 10.1016/s0923-2494(05)80096-3. View

17.

Hughes H, van Knapen F . Characterisation of a secretory antigen from Toxoplasma gondii and its role in circulating antigen production. Int J Parasitol. 1982; 12(5):433-7. DOI: 10.1016/0020-7519(82)90073-x. View

18.

Zenclussen A, Joachim R, Hagen E, Peiser C, Klapp B, Arck P . Heme oxygenase is downregulated in stress-triggered and interleukin-12-mediated murine abortion. Scand J Immunol. 2002; 55(6):560-9. DOI: 10.1046/j.1365-3083.2002.01091.x. View

19.

Tone Y, Furuuchi K, Kojima Y, Tykocinski M, Greene M, Tone M . Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat Immunol. 2007; 9(2):194-202. DOI: 10.1038/ni1549. View

20.

Ge Y, Chen J, Qiu X, Zhang J, Cui L, Qi Y . Natural killer cell intrinsic toll-like receptor MyD88 signaling contributes to IL-12-dependent IFN-γ production by mice during infection with Toxoplasma gondii. Int J Parasitol. 2014; 44(7):475-84. DOI: 10.1016/j.ijpara.2014.03.004. View