Skip to main content
SpringerLink
Log in

The Role of Soluble HLA-G in the Vertical Transmission of Toxoplasma gondii

  • MOLECULAR CELL BIOLOGY
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Soluble human leukocyte antigen G (sHLA-G) plays a key role in pregnancy through interaction with decidual natural killer (dNK) cell inhibitory receptors at the maternal-fetal interface. To demonstrate the possible role of sHLA-G during the pregnancy with Toxoplasma gondii infection, we compared the concentration of a murine functional homolog of sHLA-G, Qa-2, in T. gondii infected and non-infected pregnant C57BL/6 mice, and that of sHLA-G in BeWo culture supernatant. In addition, the levels of KIR2DL4 expressed on human dNK cells and NKG2A in pregnant mice were evaluated. We showed that T. gondii infection result in significant increase in the level of Qa-2 and NKG2A in pregnant mice. sHLA-G and KIR2DL4 in human samples were also significantly upregulated under the condition of T. gondii infection. The further treatment with sHLA-G antibody could reduce the expression level of KIR2DL4 which was upregulated by T. gondii infection. In summary, sHLA-G could upregulate the expression level of KIR2DL4 which lead to excessive immunological tolerance, and further contributed to T. gondii immunity escaping and affecting fetus via vertical transmission which may lead to adverse outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.

Similar content being viewed by others

REFERENCES

  1. Mahalakshmi B., Therese K.L., Devipriya U., Pushpa-latha V., Margarita S., Madhavan H.N. 2010. Infectious aetiology of congenital cataract based on TORCHES screening in a tertiary eye hospital in Chennai, Tamil Nadu, India. Indian J. Med. Res. 131, 559–564.

    CAS  PubMed  Google Scholar 

  2. Bessières M.H., Berrebi A., Rolland M., Bloom M.C., Roques C., Cassaing S., Courjault C., Séguéla J.P. 2001. Neonatal screening for congenital toxoplasmosis in a cohort of 165 women infected during pregnancy and influence of in utero treatment on the results of neonatal tests. Eur. J. Obstet. Gynecol. Reprod. Biol. 94, 37–45.

    Article  PubMed  Google Scholar 

  3. Abbasi M., Kowalewska-Grochowska K., Bahar M.A., Kilani R.T., Winkler-Lowen B., Guilbert L.J. 2003. Infection of placental trophoblasts by Toxoplasma gondii. J. Infect. Dis. 188, 608–616.

    Article  PubMed  Google Scholar 

  4. Tarrade A., Lai Kuen R., Malassine A. 2001. Characterization of human villous and extravillous trophoblasts isolated from first trimester placenta. Lab. Invest. 8l, 1199–1211.

    Article  Google Scholar 

  5. Sipak-Szmigiel O., Ronin-Walknowska E., Cybulski C., Plonka T., Lubiński J. 2007. Antigens HLA-G, sHLA-G and sHLA-class I in reproductive failure. Folia Histochem. Cytobiol. 45, S137–141.

    PubMed  Google Scholar 

  6. Pfeiffer K.A., Rebmann V., Pässler M., van der Ven K., van der Ven H., Krebs D., Grosse-Wilde H. 2000. Soluble HLA levels in early pregnancy after in vitro fertilization. Hum. Immunol. 61, 559–564.

    Article  CAS  PubMed  Google Scholar 

  7. Rebmann V., Switala M., Eue I., Grosse-Wilde H. 2010. Soluble HLA-G is an independent factor for the prediction of pregnancy outcome after ART: A German multi-centre study. Hum. Reprod. 25, 1691–1698.

    Article  CAS  PubMed  Google Scholar 

  8. Lee M., Choi B., Kwon H.J., Shim J.A., Park K.S., Lee E.S., Sohn S. 2010. The role of Qa-2, the functional homolog of HLA-G, in a Behcet’s disease-like mouse model induced by the herpes virus simplex. J. Inflamm. (Lond.). 7, 31–42.

    Article  CAS  Google Scholar 

  9. Lindaman A., Dowden A., Zavazava N. 2006. Soluble HLA-G molecules induce apotosis in natural killer cells. Am. J. Peprod. Immunol. 56, 68–76.

    Article  CAS  Google Scholar 

  10. Park G.M., Lee S., Park B., Kim E., Shin J., Cho K., Ahn K. 2004. Soluble HLA-G generated by proteolytic shedding inhibits NK-mediated cell lysis. Biochem. Biophys. Res. Commun. 3, 606–611.

    Article  CAS  Google Scholar 

  11. Riley J.K., Yokoyama W.M. 2008. NK cell tolerance and the maternal–fetal interface. Am. J. Reprod. Immunol. 59, 371–387.

    Article  PubMed  Google Scholar 

  12. Morandi F., Ferretti E., Castriconi R., Dondero A., Petretto A., Bottino C., Pistoia V. 2011. Soluble HLA-G dampens CD94/NKG2A expression and function and differentially modulates chemotaxis and cytokine and chemokine secretion in CD56bright and CD56dim NK cells. Blood. 118, 5840–5850.

    Article  CAS  PubMed  Google Scholar 

  13. Zhao M., Zhang R., Xu X., Liu Y., Zhang H., Zhai X., Hu X. 2013. IL-10 reduces levels of apoptosis in Toxoplasma gondii-infected trophoblasts. PLoS One. 8, e56455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Barbosa B.F., Silva D.A., Costa I.N., Mineo J.R., Ferro E.A. 2008. BeWo trophoblast cell susceptibility to Toxoplasma gondii is increased by interferon-gamma, interleukin-10 and transforming growth factor-beta1. Clin. Exp. Immunol. 151, 536–545.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cowen D., Wolf A. 1950. Experimental congenital toxoplasmosis: 2. Transmission of toxoplasmosis to the placenta and fetus following vaginal infection in the pregnant mouse. J. Exp. Med. 92, 403–416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Weng P.J., Fu Y.M., Ding S.X., Xu D.P., Lin A., Yan W.H. 2011. Elevation of plasma soluble human leukocyte antigen-G in patients with chronic hepatitis C virus infection. Hum. Immunol. 72, 406–411.

    Article  CAS  PubMed  Google Scholar 

  17. Celsi F., Catamo E., Kleiner G., Tricarico P.M., Vuch J., Crovella S. 2013. HLA-G/C, miRNAs, and their role in HIV infection and replication. Biomed. Res. Int. 2013, 693646.

    Article  CAS  Google Scholar 

  18. Thibodeau V., Lajoie J., Labbé A.-C., Zannou M.D., Fowke K.R., Alary M., Poudrier J., Roger M. 2011. High level of soluble HLA-G in the female genital tract of Beninese commercial sex workers is associated with HIV-1 infection. PLoS One. 6, e25185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. d’Almeida T.C., Sadissou I., Milet J., Cottrell G., Mondière A., Avokpaho E., Gineau L., Sabbagh A., Massougbodji A., Moutairou K., Donadi E.A., Favier B., Carosella E., Moreau P., Rouas-Freiss N., et al. 2017. Soluble human leukocyte antigen-G during pregnancy and infancy in Benin: Mother/child resemblance and association with the risk of malaria infection and low birth weight. PLoS One. 12, e0171117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sadissou I., d’Almeida T., Cottrell G., Luty A., Krawice-Radanne I., Massougbodji A., Moreau P., Moutairou K., Malar J. 2014. High plasma levels of HLA-G are associated with low birth weight and with an increased risk of malaria in infancy. Malar. J. 13, 312–319.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Robert-Gangneux F., Gangneux J.P., Vu N., Jaillard S., Guiguen C., Amiot L. 2011. High level of soluble HLA-G in amniotic fluid is correlated with congenital transmission of Toxoplasma gondii. Clin. Immunol. 138, 129–134.

    Article  CAS  PubMed  Google Scholar 

  22. Kusanovic J.P., Romero R., Jodicke C., Mazaki-Tovi S., Vaisbuch E., Erez O., Mittal P., Gotsch F., Chaiworapongsa T., Edwin S.S., Pacora P., Hassan S.S. 2009. Amniotic fluid soluble human leukocyte antigen-G in term and preterm parturition, and intra-amniotic infection/inflammation. J. Matern. Fetal. Neonatal. Med. 22, 1151–1166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Salcedo M., Bousso P., Ljunggren H.G., Kourilsky P., Abastado J.P. 1998. The Qa-1b molecule binds to a large subpopulation of murine NK cells. Eur. J. Immunol. 28, 4356–4361.

    Article  CAS  PubMed  Google Scholar 

  24. Xu X., Fu Q., Zhang Q., Zhao M., Gao Z., Liu X., Liu Y., Hu X. 2013. Changes of human decidual natural killer cells cocultured with YFP-Toxoplasma gondii: Implications for abnormal pregnancy. Fertil. Steril. 99, 427–432.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, Binzhou Medical University, 264003, Yantai, Shandong Province, China

    H. F. Wang, Y. Z. Jiang, X. B. Liu, H. X. Zhang & X. M. Hu

  2. Medical and Pharmaceutical Research Center, Binzhou Medical University, 264003, Yantai, Shandong Province, China

    L. Q. Ren & X. M. Hu

  3. Department of Immunology, Shandong College of Traditional Chinese Medicine, 264003, Yantai, Shandong Province, China

    H. F. Wang

Authors
  1. H. F. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Z. Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Q. Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. X. B. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. X. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. X. M. Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to X. M. Hu.

Additional information

The text was submitted by the author(s) in English.

These authors contributed equally to the work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H.F., Jiang, Y.Z., Ren, L.Q. et al. The Role of Soluble HLA-G in the Vertical Transmission of Toxoplasma gondii. Mol Biol 53, 267–273 (2019). https://doi.org/10.1134/S002689331902016X

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S002689331902016X

Keywords:

Search

Navigation