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Induction of IL-12 production in human peripheral monocytes by Trypanosoma cruzi Is mediated by glycosylphosphatidylinositol-anchored mucin-like glycoproteins and potentiated by IFN- γ and CD40-CD40L interactions.

Abel LC, Ferreira LR, Cunha Navarro I, Baron MA, Kalil J, Gazzinelli RT, Rizzo LV, Cunha-Neto E - Mediators Inflamm. (2014)

Bottom Line: It has been extensively described that T. cruzi or its products-like GPI anchors isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI-mucins)-are potent inducers of proinflammatory responses (i.e., cytokines and NO production) by IFN-γ primed murine macrophages.However, little is known about whether T. cruzi or GPI-mucins exert a similar action in human cells.We observed that both living T. cruzi trypomastigotes and tGPI-mucins are potent inducers of IL-12 by human peripheral blood monocytes and this effect depends on CD40-CD40L interaction and IFN-γ.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, Brazil.

ABSTRACT
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is characterized by immunopathology driven by IFN-γ secreting Th1-like T cells. T. cruzi has a thick coat of mucin-like glycoproteins covering its surface, which plays an important role in parasite invasion and host immunomodulation. It has been extensively described that T. cruzi or its products-like GPI anchors isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI-mucins)-are potent inducers of proinflammatory responses (i.e., cytokines and NO production) by IFN-γ primed murine macrophages. However, little is known about whether T. cruzi or GPI-mucins exert a similar action in human cells. We therefore decided to further investigate the in vitro cytokine production profile from human mononuclear cells from uninfected donors exposed to T. cruzi as well as tGPI-mucins. We observed that both living T. cruzi trypomastigotes and tGPI-mucins are potent inducers of IL-12 by human peripheral blood monocytes and this effect depends on CD40-CD40L interaction and IFN-γ. Our findings suggest that the polarized T1-type cytokine profile seen in T. cruzi infected patients might be a long-term effect of IL-12 production induced by lifelong exposure to T. cruzi tGPI-mucins.

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T. cruzi-induced IL-12 production is potentiated by activated T cells. Results come from 4 distinct experiments. Groups were compared by a nonparametrical test (Mann-Whitney Rank Sum Test) with GraphPad InStat software (version 5.0; GraphPad). Results were expressed as medians and interquartile ranges. P values were considered significant if <0.05.
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fig2: T. cruzi-induced IL-12 production is potentiated by activated T cells. Results come from 4 distinct experiments. Groups were compared by a nonparametrical test (Mann-Whitney Rank Sum Test) with GraphPad InStat software (version 5.0; GraphPad). Results were expressed as medians and interquartile ranges. P values were considered significant if <0.05.

Mentions: To further investigate the phenomenon observed in the endomyocardial biopsies wells we assayed cytokine production in supernatants of human PBMC in the presence of living T. cruzi and/or PHA-activated T cells. As shown in Figure 2, T. cruzi trypomastigotes can induce moderate production of IL-12 directly on irradiated PBMC or in cocultures of PBMC and T cells. However, coculture with PHA-activated T cell lines induced a 10- to 100-fold increase in IL-12 production by irradiated PBMC.


Induction of IL-12 production in human peripheral monocytes by Trypanosoma cruzi Is mediated by glycosylphosphatidylinositol-anchored mucin-like glycoproteins and potentiated by IFN- γ and CD40-CD40L interactions.

Abel LC, Ferreira LR, Cunha Navarro I, Baron MA, Kalil J, Gazzinelli RT, Rizzo LV, Cunha-Neto E - Mediators Inflamm. (2014)

T. cruzi-induced IL-12 production is potentiated by activated T cells. Results come from 4 distinct experiments. Groups were compared by a nonparametrical test (Mann-Whitney Rank Sum Test) with GraphPad InStat software (version 5.0; GraphPad). Results were expressed as medians and interquartile ranges. P values were considered significant if <0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4120781&req=5

fig2: T. cruzi-induced IL-12 production is potentiated by activated T cells. Results come from 4 distinct experiments. Groups were compared by a nonparametrical test (Mann-Whitney Rank Sum Test) with GraphPad InStat software (version 5.0; GraphPad). Results were expressed as medians and interquartile ranges. P values were considered significant if <0.05.
Mentions: To further investigate the phenomenon observed in the endomyocardial biopsies wells we assayed cytokine production in supernatants of human PBMC in the presence of living T. cruzi and/or PHA-activated T cells. As shown in Figure 2, T. cruzi trypomastigotes can induce moderate production of IL-12 directly on irradiated PBMC or in cocultures of PBMC and T cells. However, coculture with PHA-activated T cell lines induced a 10- to 100-fold increase in IL-12 production by irradiated PBMC.

Bottom Line: It has been extensively described that T. cruzi or its products-like GPI anchors isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI-mucins)-are potent inducers of proinflammatory responses (i.e., cytokines and NO production) by IFN-γ primed murine macrophages.However, little is known about whether T. cruzi or GPI-mucins exert a similar action in human cells.We observed that both living T. cruzi trypomastigotes and tGPI-mucins are potent inducers of IL-12 by human peripheral blood monocytes and this effect depends on CD40-CD40L interaction and IFN-γ.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, Brazil.

ABSTRACT
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is characterized by immunopathology driven by IFN-γ secreting Th1-like T cells. T. cruzi has a thick coat of mucin-like glycoproteins covering its surface, which plays an important role in parasite invasion and host immunomodulation. It has been extensively described that T. cruzi or its products-like GPI anchors isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI-mucins)-are potent inducers of proinflammatory responses (i.e., cytokines and NO production) by IFN-γ primed murine macrophages. However, little is known about whether T. cruzi or GPI-mucins exert a similar action in human cells. We therefore decided to further investigate the in vitro cytokine production profile from human mononuclear cells from uninfected donors exposed to T. cruzi as well as tGPI-mucins. We observed that both living T. cruzi trypomastigotes and tGPI-mucins are potent inducers of IL-12 by human peripheral blood monocytes and this effect depends on CD40-CD40L interaction and IFN-γ. Our findings suggest that the polarized T1-type cytokine profile seen in T. cruzi infected patients might be a long-term effect of IL-12 production induced by lifelong exposure to T. cruzi tGPI-mucins.

Show MeSH
Related in: MedlinePlus