Toxoplasma gondii Infection of Decidual CD1c+ Dendritic Cells Enhances Cytotoxicity of Decidual Natural Killer Cells
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There is crosstalk between decidual natural killer (dNK) cells and decidual dendritic cells (dDCs) that promotes tolerance of trophoblast cells carrying paternally derived antigens. In the present study, we report that infection of CD1c+ dDCs with Toxoplasma gondii enhanced gamma interferon (IFN-γ) production by dNK cells in co-culture. The enhancement of IFN-γ production was induced by cytokine IL-12 which increased obviously in co-culture of dDCs with dNK cells following T. gondii infection, and this enhancement largely abrogated when cells were cultured in the presence of an anti-IL-12 antibody. The expression of KIR2DL4 and NKG2D on dNK cells was increased after T. gondii infection, and higher expression of NKG2D was induced by co-cultured dDCs. Neutralization of IL-12 decreased NKG2D expression on dNK cells. Furthermore, dDCs with T. gondii infection increased the cytotoxicity of co-cultured dNK cells against K562 target cells, which was mediated by activating receptor of NKG2D. Thus, T. gondii infection of dDCs enhanced dNK cell IFN-γ production and NKG2D expression, and then led to increased cytotoxicity of dNK cells. The up-regulated dNK cell cytotoxicity at the maternal–fetal interface may contribute to abnormal pregnancy outcomes caused by T. gondii infection in early pregnancy.
KEY WORDSToxoplasma gondii dDCs dNK cells cytotoxicity mechanism of adverse pregnancy outcomes
This study was supported by funds from the National Natural Science Foundation of China (81171591 and 81273243), the Natural Science Foundation of Shandong Province (ZR2010HM012), and the Science and Technology Development Planning Project of Shan dong Province (2012GSF11809). We thank Professor Zheng Jing for providing human tissues samples from Yantai Chinese Medicine Hospital.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 3.Senegas, A., O. Villard, A. Neuville, L. Marcellin, A.W. Pfaff, T. Steinmetz, M. Mousli, J.P. Klein, and E. Candolfi. 2009. Toxoplasma gondii-induced foetal resorption in mice involves interferon-gamma-induced apoptosis and spiral artery dilation at the maternofoetal interface. International Journal for Parasitology 39: 481–487.PubMedCrossRefGoogle Scholar
- 8.Crncic, T.B., G. Laskarin, K.J. Frankovic, V.S. Tokmadzic, N. Strbo, I. Bedenicki, P. Le Bouteiller, J. Tabiasco, and D. Rukavina. 2007. Early pregnancy decidual lymphocytes beside perforin use Fas ligand (FasL) mediated cytotoxicity. Journal of Reproductive Immunology 73: 108–117.PubMedCrossRefGoogle Scholar
- 10.Yamada, H., E.H. Kato, G. Kobashi, Y. Ebina, S. Shimada, M. Morikawa, N. Sakuragi, and S. Fujimoto. 2001. High NK cell activity in early pregnancy correlates with subsequent abortion with normal chromosomes in women with recurrent abortion. American Journal of Reproductive Immunology 46: 132–136.PubMedCrossRefGoogle Scholar
- 11.Goldszmid, R.S., A. Bafica, D. Jankovic, C.G. Feng, P. Caspar, R. Winkler-Pickett, G. Trinchieri, and A. Sher. 2007. TAP-1 indirectly regulates CD4+ T cell priming in Toxoplasma gondii infection by controlling NK cell IFN-gamma production. Journal of Experimental Medicine 204: 2591–2602.PubMedCentralPubMedCrossRefGoogle Scholar
- 14.Kämmerer, U., A.O. Eggert, M. Kapp, A.D. McLellan, T.B. Geijtenbeek, J. Dietl, Y. van Kooyk, and E. Kämpgen. 2003. Unique appearance of proliferating antigen-presenting cells expressing DC-SIGN (CD209) in the decidua of early human pregnancy. American Journal of Pathology 162: 887–896.PubMedCentralPubMedCrossRefGoogle Scholar
- 18.Liu, C.H., Y.T. Fan, A. Dias, L. Esper, R.A. Corn, A. Bafica, F.S. Machado, and J. Aliberti. 2006. Cutting edge: dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice. Journal of Immunology 177: 31–35.CrossRefGoogle Scholar
- 21.Blois, S.M., G. Barrientos, M.G. Garcia, A.S. Orsal, M. Tometten, R.I. Cordo-Russo, B.F. Klapp, A. Santoni, N. Fernández, P. Terness, and P.C. Arck. 2008. Interaction between dendritic cells and natural killer cells during pregnancy in mice. Journal of Molecular Medicine 86: 837–852.PubMedCrossRefGoogle Scholar
- 29.Mailliard, R.B., Y.I. Son, R. Redlinger, P.T. Coates, A. Giermasz, P.A. Morel, W.J. Storkus, and P. Kalinski. 2003. Dendritic cells mediate NK cell help for Th1 and CTL responses: two-signal requirement for the induction of NK cell helper function. Journal of Immunology 171: 2366–2373.CrossRefGoogle Scholar
- 34.Varla-Leftherioti, M., M. Spyropoulou-Vlachou, T. Keramitsoglou, M. Papadimitropoulos, C. Tsekoura, O. Graphou, C. Papadopoulou, M. Gerondi, and C. Stavropoulos-Giokas. 2005. Lack of the appropriate natural killer cell inhibitory receptors in women with spontaneous abortion. Human Immunology 66: 65–71.PubMedCrossRefGoogle Scholar
- 38.Castriconi, R., C. Cantoni, M. Della Chiesa, M. Vitale, E. Marcenaro, R. Conte, R. Biassoni, C. Bottino, L. Moretta, and A. Moretta. 2003. Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 100: 4120–4125.PubMedCentralPubMedCrossRefGoogle Scholar