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Stimulation of the trypanocidal and endoribonuclease activities by the interferon induced (2'-5') oligoadenylates
1Department of Molecular Biology, Universidad Autónoma, Canto Blanco, Madrid, Spain.
Abstract:
Interferon or 2'-5' oligoadenylates (2'-5' An) activated the microbicidal activity of primary cultures of rat glia cells and of the mouse macrophage transformed cell line J774 against infection by Trypanosoma cruzi. Pretreatment with gamma-interferon (gamma-IFN) or 2'-5' A3 of rat glia cells or direct addition of these compounds during the incubation with the parasite enhanced the uptake of metacyclic trypanosomes by the cells. Furthermore, glia cells treated with gamma-IFN or 2'-5' A3 were able to restrict the growth and to eventually destroy intracellular amastigotes. Bacterial lipopolysaccharide (LPS) synergized with gamma-IFN as well as with 2'-5' A3 and 2'-5' A4, but not with dephosphorylated 'core' molecules or ATP, to induce a partial trypanocidal activity in J774 cells. In addition, those treatments with gamma-IFN or 2'-5' A3 activated to a similar extent an endoribonuclease, which degraded ribosomal RNA, in rat glia cells, suggesting a role of this enzyme in the mechanism of the trypanocidal activity of gamma-IFN.
Insights
Interferon (IFN) and 2'-5' oligoadenylates (2'-5' An) enhance microbicidal activity against Trypanosoma cruzi in glial and macrophage cells. These compounds promote parasite uptake and intracellular destruction, suggesting a role for endoribonuclease in this immune response.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Trypanosoma cruzi infection poses a significant health challenge.
- Glial cells and macrophages are key immune cells involved in host defense.
- Interferon and 2 -5 oligoadenylates are known immune modulators.
Purpose of the Study:
- To investigate the effect of interferon (IFN) and 2 -5 oligoadenylates (2 -5 An) on microbicidal activity against Trypanosoma cruzi.
- To determine if these compounds enhance parasite uptake and intracellular destruction by host cells.
- To explore the role of endoribonuclease in the observed trypanocidal activity.
Main Methods:
- Primary cultures of rat glia cells and the J774 macrophage cell line were used.
- Cells were pretreated or incubated with gamma-interferon (gamma-IFN) or various 2 -5 An compounds.
- Parasite uptake, intracellular amastigote growth, and endoribonuclease activity were assessed.
- Bacterial lipopolysaccharide (LPS) was used in combination with IFN and 2 -5 An.
Main Results:
- Gamma-IFN and 2 -5 A3 significantly enhanced the uptake of metacyclic trypanosomes by glia cells.
- Treated glia cells restricted the growth and destroyed intracellular amastigotes.
- LPS synergized with gamma-IFN and 2 -5 An to induce partial trypanocidal activity in J774 cells.
- Both gamma-IFN and 2 -5 A3 activated endoribonuclease, degrading ribosomal RNA in glia cells.
Conclusions:
- Interferon and 2 -5 oligoadenylates activate microbicidal activity against Trypanosoma cruzi in glial and macrophage cells.
- These compounds enhance parasite uptake and intracellular killing, suggesting a novel therapeutic approach.
- Activation of endoribonuclease is implicated in the mechanism of IFN-mediated trypanocidal activity.