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Hepatic stellate cells (HSCs) are considered as the main effector cells in vitamin A metabolism and liver fibrosis, as well as in hepatic immune regulation. Recently, researches have revealed that HSCs have plasticity and heterogeneity, which depend on their lobular location and whether liver is normal or injured. This research aimed to explore the biological characteristics and heterogeneity of HSCs in mice with Schistosoma japonicum ( S. japonicum ) infection, and determine the subpopulation of HSCs in pathogenesis of hepatic fibrosis caused by S. japonicum infection. Results revealed that HSCs significantly increased the expressions of MHC II and fibrogenic genes after S. japonicum infection, and could be classified into MHC II + HSCs and MHC II − HSCs subsets. Both two HSCs populations suppressed the proliferation of activated CD4 + T cells, whereas only MHC II − HSCs displayed a myofibroblast-like phenotype. In response to IFN-γ, HSCs up-regulated the expressions of MHC II and CIITA , while down-regulated the expression of fibrogenic gene Col1 . In addition, praziquantel treatment decreased the expressions of fibrogenic genes in MHC II − HSCs. These results confirmed that HSCs from S. japonicum -infected mice have heterogeneity. The MHC II − α-SMA + HSCs were major subsets of HSCs contributing to liver fibrosis and could be considered as a potential target of praziquantel anti-fibrosis treatment. [ABSTRACT FROM AUTHOR]

Angiostrongylus cantonensis is a neurotropic parasite which can cause injury to central nervous system and eosinophilic meningitis to human. Natural killer (NK) cells are specialized innate lymphocytes important in early defense against pathogens as in a variety of intracellular bacterial, viral, and protozoan infections. However, the number and function of NK cells in extracellular parasitic infection of A. cantonensis are unclear. In this study, on A. cantonensis infected mice which may mimic the human's infection, we found that the percentage of splenic NK cells and the absolute number of peripheral blood NK cells were decreased at 21-day post infection compared with that of controls. When administrating with albendazole treatment at early stage of the infection, the changes of NK cells could be avoided. Further analysis confirmed that the reduction of NK cells was due to their apoptosis manifested as increased expressions of annexin V and activated caspase-3 after 16-day post infection. Moreover, both activated and inhibitory receptors such as CD16, CD69, NKG2D, and Ly49a on NK cells were down-regulated after 16-day post infection. Interestingly, NK cells isolated from mice of 21-day post infection showed enhanced IFN-γ production when stimulated with IL-12 for 24 h and cytotoxicity to YAC-1 cells, as well as elevated CD107a expression. It is evident that NK cell population and its function were changed in A. cantonensis infected mice, suggesting their involvement in pathogenesis of the infection. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is an opportunistic intracellular parasite that is highly prevalent in human and warm-blooded animals throughout the world, leading to potentially severe congenital infections. Although the abortion caused by T. gondii is believed to be dependent on the timing of maternal infection during pregnancy, the mechanism remains unclear. This study was focused on the effects of T. gondii excreted-secreted antigens on pregnant outcomes and CD4+CD25+ Foxp3+ regulatory T cells at different stages of pregnancy. The results showed that in mice the frequency and suppressive function of CD4+CD25+ regulatory cells were diminished after injection of T. gondii excreted-secreted antigens at early and intermediate stages of pregnancy. The abortion caused by T. gondii excreted-secreted antigens at early pregnancy could be partly prevented by adoptively transferring of CD4+CD25+ cells from the mice injected with T. gondii excreted-secreted antigens at late pregnancy, but not from the mice with the same treatment at early pregnancy. Furthermore, T. gondii excreted-secreted antigens induced apoptosis of CD4+CD25+ regulatory cells of mice in early and intermediate stages of pregnancy by down-regulating their Bcl-2 expressions and Bcl-2/Bax ratio. This study provides new insights into the mechanism that T. gondii infection is the high risk factor for abortion in early pregnancy. [ABSTRACT FROM AUTHOR]

Background: Immunosuppression has been described as a consequence of brain injury and infection by different mechanisms. Angiostrongylus cantonensis can cause injury to the central nervous system and eosinophilic meningitis to human. Both T cell and B cell immunity play an essential role in the resistance of the infection. However, whether brain injury caused by A. cantonensis infection can lead to immunosuppression is not clear. Therefore, the present study sought to observe the alteration of immune responses in mice infected with A. cantonensis.Methods: Mice were infected with 20 third-stage A. cantonensis larvae. The messenger RNA (mRNA) expression of inflammatory mediators in brain tissues was observed by qRT-PCR. Cell surface markers including CD3, CD4, CD8, CD19, B220, 7-AAD, annexin-V, IgM, AA4.1, and CD23 were evaluated by using flow cytometry. The immune functions of T and B lymphocytes were detected upon stimulation by ConA and antibody responses to a nonself antigen OVA, respectively. Activation of the hypothalamic-pituitary-adrenal axis was evaluated by analyzing the concentration of plasma corticosterone and levels of mRNA for corticotropin-releasing hormone, tyrosine hydroxylase, and c-fos.Results: A. cantonensis infection results in obvious immunosuppression evidenced as progressive spleen and thymus atrophy and significant decrease in the number of lymphocyte subsets including B cells, CD3+ T cells, CD4+ T cells, and CD8+ T cells, as well as reduced T cell proliferation at 21 days post-infection and antibody reaction to exogenous protein after infection. However, the sharp decrease of splenic and thymic cells was not due to cell apoptosis but to B cell genesis cessation and impairing thymocyte development. In addition, helminthicide treatment with albendazole on infected mice at 7 days post-infection could prevent immunosuppressive symptoms. Importantly, infected mice displayed hypothalamic-pituitary-adrenal axis activation, with peak responses occurring at 16 days post-infection, and glucocorticoid receptor antagonist could partially restore the infection-induced cessation of B cell genesis.Conclusions: Brain injury caused by A. cantonensis infection, like that of brain stroke and trauma, enhanced endogenous corticosteroid activity, resulting in peripheral immunosuppression. [ABSTRACT FROM AUTHOR]