Cellular and humoral peritoneal immunity to Mesocestoides vogae metacestode infection in mice

Abstract

Background Here, Mesocestoides (M.) vogae infection in mice is proposed as a suitable experimental model for studying the immunity in the peritoneal cavity of mice. Methods To investigate the kinetics of immune parameters in M. vogae-infected mice, we detected, using flow cytometry, the expression of selected lymphoid and myeloid markers within the peritoneal cell population at day 0, 3, 6, 10, 14, 19, 25, 30 and 35 post-infection. Then, using ELISA, we analyzed the cytokine IFN-γ, TGF-β, IL-4 and IL-10 responses and the levels of anti-M. vogae IgG and IgM antibodies in the peritoneal lavage fluid. Cells isolated from the peritoneal cavity were subjected to further molecular analysis. To assess cell activation, peritoneal cells were exposed to LPS, and culture supernatants were collected and assayed for the level of cytokines and production of nitrite. Ly6C+ and Ly6G+ cells were isolated using MACS from the peritoneal cells at day 35 post-infection. Both MACS-isolated subsets were co-cultured with preactivated T cells to measure their suppressive capacity. Next, the role of parasite excretory-secretory antigens in induction of CD11b+ myeloid cells with the suppressive phenotype and the production of IL-10 was examined. Results In the peritoneal cavity an initial increase of CD11b+Gr-1+F4/80highMHC IIhigh cells, NK, NKT cells and CD8+ cytotoxic T cells was observed in the first week of infection. At day 14 post-infection, an increase in the number of myeloid CD11b+Gr-1+ cells was detected, and most of this cell population expressed low levels of F4/80 and MHC II in later stages of infection, suggesting the impairment of antigen-presenting cell functions, probably through the excretory-secretory molecules. Moreover, we confirmed that peritoneal Gr1+ cells (Ly6C+ and Ly6G+ population) are phenotypically and functionally consistent with myeloid-derived suppressor cells. Metacestode infection elicited high levels of IL-10 and upregulated STAT-3 in peritoneal cells. A higher level of IgM suggests that this isotype may be predominant and is involved in the host protection. Conclusions Mesocestoides vogae tetrathyridia induced the recruitment of immunosuppressive cell subsets, which may play a key role in the downregulation of immune response in long-term parasitic diseases, and excretory-secretory antigens seem to be the main regulatory factor.

Co-Treatment with Human Leukocyte Extract and Albendazole Stimulates Drug’s Efficacy and Th1 Biased Immune Response in Mesocestoides vogae (Cestoda) Infection via Modulation of Transcription Factors, Macrophage Polarization, and Cytokine Profiles

“…They are also used in veterinary medicine. In the current study, we evaluated the impact of ABZ and DLE administration on the inflammatory responses and larval counts in the peritoneal cavity utilizing the M. vogae mouse model, where larvae asexually reproduce despite a robust immune response from the mouse hosts [ 26 , 28 ]. In our study, the highest reduction was observed after combined treatment with both drugs, suggesting that DLE, although being non-larvicidal in vitro (unpublished observations), enhanced the drug´s efficacy via the activation of antiparasitic immunity.…”

“…Recently, we showed that STAT1 gene expression in PECs was gradually downregulated while transcript levels for STAT3, STAT6, and IL-10 were markedly elevated within the course of M. vogae infection in mice [ 28 ]. The binding of IL-10 activates a cascade of molecules including the STAT3 factor required for the anti-inflammatory effects of IL-10 [ 51 ].…”

“…Adherent macrophages/monocytes were analyzed for mRNA abundance of transcription factors STAT1, STAT3, and STAT6, IFN-γ receptor (IFN-γR), IL-12p40, and IL-10. Moreover, mRNAs isolated from adherent PECs from infected mice after cultivation with ABZ, ABZ-SO, and DLE were examined for the expression of IFN-γ, IL-12p40, IL-10, arginase 1, iNOS, NF-κB, and IFN-γ receptor as previously described [ 28 ]. Total RNA was extracted from the cell using RiboZol reagent (VWR Life Science, Radnor Corporate Center, Radnor, PA, USA).…”

Differential activity of human leukocyte extract on systemic immune response and cyst growth in mice with Echinococcus multilocularis infection after oral, subcutaneous and intraperitoneal routes of administration

“…The effects of IP-administered DLE alone and as the adjuvant with albendazole were investigated during infection of mice with proliferating metacestodes of Mesocestoides vogae . DLE increased the larvicidal effect of albendazole on the parasites in the livers and the peritoneal cavities, stimulated the proliferation of T lymphocytes, and modified the serum cytokine profiles towards the balanced Th1/Th2 type ( Mačak Kubašková et al ., 2018 ).…”

“…Dialyzable leukocyte extract (DLE), available under the commercial name IMMODIN (ImunaPharm, Ltd. Slovakia) is the cell homogenate prepared from desintegrated blood leukocytes of healthy human donors. In our previous studies we have shown that this type of DLE administered as an adjuvant to ABZ enhanced the drug´s efficacy via stimulation of Th1 and attenuation of Th2/Treg biased immune responses in mice infected with model metacestodes of Mesocestoides vogae ( Mačak Kubašková et al ., 2018 ). DLEs of human and animal origin typically consist of various biologically active components, which include cyclic nucleotides, nicotinamide, purine bases, histamine, ascorbates, prostaglandins, serotonin, amino acids, proteins, etc.…”