IL-10 Reduces Levels of Apoptosis in Toxoplasma gondii-Infected Trophoblasts

Background To analyze the effects of IL-10 on the HLA-G expression and the apoptosis of trophoblasts infected with Toxoplasma gondii. Methods T. gondii-infected or uninfected human trophoblasts and immortalized human placental BeWo cells were cultured with or without human IL-10. Uninfected and infected cells without IL-10 cells served as controls. HLA-G expression was measured by real-time PCR and flow cytometry, respectively. Cells apoptosis were analyzed by flow cytometry. Apoptosis associated moleculars were measured by real-time PCR and Western bolt. Results HLA-G expression was increased in the infected trophoblasts and BeWo cells compared to uninfected cells. Treatment of infected cells with IL-10 decreased HLA-G expression compared to infected cells while no change in treatment of uninfected cells compared with uninfected cells. Levels of apoptosis and apoptosis associated caspase-3 and caspase-8 decreased and c-FLIP levels increased in treated infected cells with IL-10 compared to infected cells and no difference in IL-10 treated uninfected cells compared to uninfected cells. Conclusions IL-10 regulates HLA-G expression in T. gondii-infected trophoblasts. IL-10 treatment of infected trophoblasts reduced levels of apoptosis. This may contribute to the improvement in pregnancy outcomes when women infected with T. gondii treated with IL-10.

[1]  Xue Zhou,et al.  A novel bridge between oxidative stress and immunity: the interaction between hydrogen peroxide and human leukocyte antigen G in placental trophoblasts during preeclampsia. , 2012, American journal of obstetrics and gynecology.

[2]  A. Elfayomy,et al.  Expression pattern of tumor necrosis factor alpha in placentae of idiopathic fetal growth restriction , 2012, Journal of Molecular Histology.

[3]  Q. Fu,et al.  The Immunoprotective Role of Interleukin-10 in Abnormal Pregnancy Outcome Induced by Toxoplasma gondii Infection , 2011, Gynecologic and Obstetric Investigation.

[4]  Xiao-Guang Chen,et al.  Toxoplasma gondii: the effects of infection at different stages of pregnancy on the offspring of mice. , 2011, Experimental parasitology.

[5]  M. Burnier,et al.  Ocular toxoplasmosis: an update and review of the literature. , 2009, Memorias do Instituto Oswaldo Cruz.

[6]  Yigong Shi,et al.  FLIP and the death effector domain family , 2008, Oncogene.

[7]  E. Ferro,et al.  BeWo trophoblast cell susceptibility to Toxoplasma gondii is increased by interferon‐γ, interleukin‐10 and transforming growth factor‐β1 , 2008, Clinical and experimental immunology.

[8]  G. Schulze-Tanzil,et al.  Interleukin-10 modulates pro-apoptotic effects of TNF-α in human articular chondrocytes in vitro , 2007 .

[9]  P. Moreau,et al.  Hypoxia modulates HLA-G gene expression in tumor cells. , 2007, Human immunology.

[10]  G. Schulze-Tanzil,et al.  Interleukin-10 modulates pro-apoptotic effects of TNF-alpha in human articular chondrocytes in vitro. , 2007, Cytokine.

[11]  N. Rouas-Freiss,et al.  Modulation of HLA-G Expression in Human Neural Cells after Neurotropic Viral Infections , 2005, Journal of Virology.

[12]  P. Krammer,et al.  c-FLIPR, a New Regulator of Death Receptor-induced Apoptosis* , 2005, Journal of Biological Chemistry.

[13]  T. Mosmann,et al.  IL-10 prevents naturally occurring fetal loss in the CBA x DBA/2 mating combination, and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of IFN-τ , 1995, The Journal of Immunology.

[14]  John C. Scatizzi,et al.  IL-4 and IL-10 Inhibition of Spontaneous Monocyte Apoptosis Is Associated with Flip Upregulation , 2004, Inflammation.

[15]  J. Pablos,et al.  Intracellular Regulation of Fas-Induced Apoptosis in Human Fibroblasts by Extracellular Factors and Cycloheximide 1 , 2004, The Journal of Immunology.

[16]  L. Guilbert,et al.  Infection of placental trophoblasts by Toxoplasma gondii. , 2003, The Journal of infectious diseases.

[17]  D. Hemmings,et al.  Human cytomegalovirus-caused damage to placental trophoblasts mediated by immediate-early gene-induced tumor necrosis factor-alpha. , 2002, The American journal of pathology.

[18]  N. Mitsiades,et al.  Regulation of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in thyroid carcinoma cells. , 2002, The American journal of pathology.

[19]  J. Dietl,et al.  Th1- and Th2-like cytokine production by first trimester decidual large granular lymphocytes is influenced by HLA-G and HLA-E. , 2002, Molecular human reproduction.

[20]  V. Carruthers.  Host cell invasion by the opportunistic pathogen Toxoplasma gondii. , 2002, Acta tropica.

[21]  L. Weiss,et al.  Erratum to “Toxoplasma gondii: from animals to humans” [Int. J. Parasitol. 30 (2000) 1217–1258] , 2001 .

[22]  S. Kōzuma,et al.  Human Leukocyte Antigen‐G‐Expressing Cells Differently Modulate the Release of Cytokines from Mononuclear Cells Present in the Decidua Versus Peripheral Blood , 2001, American journal of reproductive immunology.

[23]  P. André,et al.  Modulation of HLA-G antigens expression in myelomonocytic cells. , 2000, Human immunology.

[24]  L. Weiss,et al.  Toxoplasma gondii: from animals to humans. , 2000, International journal for parasitology.

[25]  G. Salvesen,et al.  Caspase activation: the induced-proximity model. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Mortara,et al.  Calomys callosus (Rodentia: Cricetidae) trophoblast cells as host cells to Toxoplasma gondii in early pregnancy , 1999, Parasitology Research.

[27]  V. Guiard,et al.  © 1999 The Japanese Society for Immunology IL-10 selectively induces HLA-G expression in human trophoblasts and monocytes , 2022 .

[28]  T. Curiel,et al.  Toxoplasma gondii-infected cells are resistant to multiple inducers of apoptosis. , 1998, Journal of immunology.

[29]  J. Dausset,et al.  Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[30]  A. Sher,et al.  In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. , 1996, Journal of immunology.

[31]  M. Rajasilta.  Relationship between Food, Fat, Sexual Maturation, and Spawning Time of Baltic Herring (Clupea harengus membras) in the Archipelago Sea , 1992 .

[32]  I. Sargent,et al.  Localization of tumour necrosis factor production in cells at the materno/fetal interface in human pregnancy , 1992, Clinical and experimental immunology.