+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Excreted-secreted antigens of Toxoplasma gondii inhibit Foxp3 via IL-2Rγ/JAK3/Stats pathway

Excreted-secreted antigens of Toxoplasma gondii inhibit Foxp3 via IL-2Rγ/JAK3/Stats pathway

Journal of Cellular Biochemistry 119(12): 10176-10185

Toxoplasma gondii excreted-secreted antigens (ESA) could lead to the fetal abortion especially in the early stage of pregnancy. Deficit in regulatory T cells is a critical event in the fetal abortion. Transcription factor forkhead box p3 (Foxp3) mediates differentiation and functional roles on regulatory T cells. Previously, we revealed that ESA inhibited Foxp3 through the suppression of transforming growth factor-β type II receptor, phosphorylation of Smad2, Smad3, and Smad4. Knockdown of Smad2 collaborated with ESA to further inhibit Foxp3. The decrease in Foxp3 caused by ESA reversed via forced expression of Smad2, Smad3, and Smad4, respectively. In this study, we investigate whether other signaling pathways are implicated in ESA-induced Foxp3 downregulation. EL4 cells were cultured and stimulated with ESA. Interleukin-2 receptor γ (IL-2Rγ) chain, Janus kinase 3 (JAK3), signal transducer and activator of transcription 5 (Stat5), Stat3, phosphorylation of Stat5 and Stat3 were assayed by Western blot analysis. Phosphorylation of Stat5 and Stat3 was further measured by cellular immunofluorescence. The expression plasmid of pcDNA3.1-Stat3 and pcDNA3.1-Stat5b was constructed, respectively. The concentration of interleukin-2 (IL-2) in the culture supernatants was detected by enzyme-linked immunosorbent assay. ESA inhibited the level of JAK3, phosphorylation of Stat5 and Stat3, and Foxp3 in EL4 cells. The suppressive effects of ESA on Foxp3 were attenuated by forced expression of Stat5 and Stat3. In addition, ESA suppressed IL-2Rγ in EL4 cells, while IL-2Rγ agonist could markedly reverse the diminished Foxp3 caused by ESA. Furthermore, ESA directly influenced the expression of IL-2Rγ, rather than the availability of IL-2 indirectly. ESA suppressed the level of Foxp3 via inhibiting IL-2Rγ/JAK3/Stats signaling pathway in EL4 cells.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 063827250

Download citation: RISBibTeXText

PMID: 30129110

DOI: 10.1002/jcb.27358

Related references

Toxoplasma gondii excreted-secreted antigens suppress Foxp3 via PI3K-AKT-mTOR signaling pathway. Journal of Cellular Biochemistry 2019, 2019

Chinese 1 strain of Toxoplasma gondii excreted-secreted antigens negatively modulate Foxp3 via inhibition of the TGFßRII/Smad2/Smad3/Smad4 pathway. Journal of Cellular and Molecular Medicine 21(9): 1944-1953, 2017

Effects of excreted/secreted antigens of Toxoplasma gondii on CD4+ CD25+ Foxp3+ T cells and NK cells of melanoma-bearing mice. Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 23(3): 301-306, 2012

Excreted/secreted antigens of Toxoplasma gondii--their origin and role in the host-parasite interaction. Research in Immunology 144(1): 41-44, 1993

Toxoplasma gondii excreted secreted antigens first characterization and immunogenicity in human and experimental infections. Immunobiology 173(2-5): 241-242, 1986

Production of antibodies in murine mucosal immunization with Toxoplasma gondii excreted/secreted antigens. Veterinary Parasitology 128(1-2): 23-28, 2005

Nonimmunological factors affecting the release of excreted/secreted antigens from Toxoplasma gondii cysts. Zentralblatt für Bakteriologie 284(2-3): 378-389, 1996

Immune responses against excreted/secreted antigens of Toxoplasma gondii tachyzoites in the murine model. Veterinary Parasitology 113(2): 123-134, 2003

Detection in human sera to excreted secreted antigens Toxoplasma gondii by use immunoblot assay of IgG, IgM and IgA from of dot Elisa and. Annals of Tropical Medicine And Parasitology 92(1): 23-30, 1998

Interleukin-10 Serum Levels after Vaccination with In Vivo Prepared Toxoplasma gondii Excreted/Secreted Antigens. Oman Medical Journal 28(2): 112-115, 2013

Detection in human sera of IgG, IgM and IgA to excreted/secreted antigens from Toxoplasma gondii by use of dot-ELISA and immunoblot assay. Annals of Tropical Medicine and Parasitology 92(1): 23-30, 1998

Failure of mouse peritoneal macrophage activation by the purified excreted/secreted antigens of Toxoplasma gondii. Microbiology and Immunology 38(11): 909-913, 1994

Evaluation of the second fraction of excreted/secreted antigens from Toxoplasma gondii by ion exchange chromatography for serodiagnosis of toxoplasmosis in rat. Journal Of Mazandaran University Of Medical Sciences: 65, 628, 2008

Interferon-γ Induced by Toxoplasma gondii Excreted/Secreted Antigens Promotes Apoptosis of CD4+CD25+ Regulatory T Cells. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 34(3): 183-188, 2018

Immunodiagnosis in cerebrospinal fluid of cerebral toxoplasmosis and HIV-infected patients using Toxoplasma gondii excreted/secreted antigens. Diagnostic Microbiology and Infectious Disease 71(3): 279-285, 2012