<i>Taenia crassiceps</i>-Excreted/Secreted Products Induce a Defined MicroRNA Profile that Modulates Inflammatory Properties of Macrophages

Martínez-Saucedo, Diana; Ruíz-Rosado, Juan de Dios; Terrazas, César; Callejas, Blanca E.; Satoskar, Abhay R.; Partida-Sánchez, Santiago; Terrazas, Luis I.

doi:10.1155/2019/2946713

Cited by 11 publications

(15 citation statements)

References 86 publications

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“…Data showed that compared with the control group, BMDMs showed long fusiform shape in the LPS-treated group ( Figure 1B). Moreover, the expression levels of related factors including IL-1b, IL-6, IL-12 and TNF-a, as well as INOS, were significantly increased in the LPS-treated group in a dose-dependent manner ( Figure 1C, p < 0.05), which was consistent with previous reports, [30][31][32] indicating the activation of TLR4 signalling. Notably, we found that the expression level of miR-7 in BMDMs was significantly up-regulated in a dose-and time-dependent manner, and reached a peak in the presence of 100 ng/ml LPS at 12 h ( Figure 1D,E, p < 0.05).…”

Section: The Expression Of Mir-7 Is Up-regulated During Tlr4 Signallisupporting

confidence: 92%

MicroRNA‐7 negatively regulates Toll‐like receptor 4 signaling pathway through FAM177A

et al. 2020

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Toll-like receptor (TLR) 4 signalling is critical for innate immunoinflammatory response and widely triggers the development of various types of clinical diseases. MicroRNA-7 (miR-7) is well documented to play an important regulatory role in various biological events. However, the exact role of miR-7 in TLR4 signalling pathway remains to be fully elucidated. In the present study, we found that miR-7 expression in TLR4 signallingactivated bone marrow-derived macrophages (BMDMs) stimulated by LPS was dramatically increased. Importantly, miR-7 deficiency significantly enhanced the production of related inflammatory cytokines including IL-1b, IL-6 and IL-12, as well as TNF-a, on LPS-activated BMDMs, accompanied by elevated transduction of TLR4 signalling including Myd88-dependent and Myd88-independent pathways, whereas miR-7 overexpression significantly decreased the transduction of TLR4 signalling and the production of related inflammatory cytokines. Mechanistically, we identified family with sequence similarity 177, member A (FAM177A) as a novel target molecule of miR-7. Furthermore, down-regulation of FAM177A using RNAi could impair the transduction of TLR4 signalling. Finally, down-regulation of FAM177A also reversed the effect of miR-7 deficiency on TLR4 signalling transduction and production of related inflammatory cytokines on BMDMs. Therefore, we provide the new evidence that miR-7 acts as a novel negative fine-tuner in regulating TLR4 signalling pathways by targeting FAM177A, which might throw light on the basal understanding on the regulatory mechanism of TLR4 signalling and benefit the development of therapeutic strategies against related clinical diseases.

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Section: The Expression Of Mir-7 Is Up-regulated During Tlr4 Signallisupporting

confidence: 92%

MicroRNA‐7 negatively regulates Toll‐like receptor 4 signaling pathway through FAM177A

et al. 2020

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“…As the infection progressed, PEC/macrophages from infected mice also showed an impairment of their ability to secrete NO in response to LPS compared to PEC obtained during the early phase of infection ( rst week). Although M. vogae-derived products induce the expression of markers of alternative activation (YM1, Arg-1 and Fizz-1) in vivo and in vitro [4], it is likely that the parasite ES antigens play important role in regulating cytokine production by inhibiting their transcripts, as has been previously reported [37].…”

Section: Discussionmentioning

confidence: 66%

Cellular And Humoral Peritoneal Immunity To Mesocestoides Vogae Metacestodes Infection In Mice.

Kubašková¹,

Mudroňová²,

Vargová³

et al. 2020

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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 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 on 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+F4/80highMHCIIhigh 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 up-regulated of STAT-3 in peritoneal cells. A higher level of IgM suggests that this isotype may be predominant and involved in host protection.Conclusions: M. vogae tetrathyridia induced the recruitment of immunosuppressive cell subsets, which may play a key role in the down-regulation of immune response in long-term parasitic diseases, and excretory-secretory antigens seem to be the main regulatory factor.

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“…As the infection progressed, PEC/macrophages from infected mice also showed an impairment of their ability to secrete NO in response to LPS compared to PEC obtained during the early phase of infection (first week). Although M. vogae -derived products induce the expression of markers of alternative activation (YM1, Arg-1 and Fizz-1) in vivo and in vitro [ 4 ], it is likely that the parasite ES antigens play important role in regulating cytokine production by inhibiting their transcripts, as has been previously reported [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Taenia crassiceps-Excreted/Secreted Products Induce a Defined MicroRNA Profile that Modulates Inflammatory Properties of Macrophages

Cited by 11 publications

References 86 publications

MicroRNA‐7 negatively regulates Toll‐like receptor 4 signaling pathway through FAM177A

MicroRNA‐7 negatively regulates Toll‐like receptor 4 signaling pathway through FAM177A

Cellular And Humoral Peritoneal Immunity To Mesocestoides Vogae Metacestodes Infection In Mice.

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

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