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Antigen presentation capacity of murine macrophages infected with Leishmania amazonensis amastigotes
E Prina1, C Jouanne, S de Souza Lão
1Unité d'Immunophysiologie Cellulaire, Institut Pasteur, Paris, France.
Abstract:
Leishmania-infected M phi are potential candidates for the presentation of parasite Ag to Leishmania-specific CD4+ T lymphocytes. To assess whether infected cells could function as APC, we examined the ability of bone marrow-derived M phi infected with Leishmania amazonensis amastigotes to stimulate various CD4+, l-Ad- or l-Ed-restricted T-cell hybridomas specific for the bacteriophage lambda repressor cl protein, the human chorionic gonadotropin or OVA. A reduced capacity of infected M phi to present native Ag to most T-cell hybridomas tested was noted that was probably a result of a lower expression on their plasma membrane of stimulatory [la-peptide] complexes. Neither a reduced Ag uptake nor an altered Ag processing appeared to be at the origin of the partial inability of infected M phi to present Ag. As regards the level of plasma membrane la expression, no quantitative difference could be detected between uninfected and infected M phi. Moreover, after fixation with paraformaldehyde, the ability of plasma membrane la molecules to bind immunogenic peptides was apparently not reduced in infected M phi. So, these cells most likely expressed functional la molecules on their cell surface. Interestingly, infected M phi and M phi infected then cured by a treatment with a leishmanicidal compound were similarly impaired in their capacity to present native Ag or peptides to the hybridomas, and no recovery was noted even 24 h after the leishmanicidal treatment. Furthermore, infected M phi and M phi incubated with heat-killed amastigotes or with an amastigote homogenate exhibited similar inhibitions of Ag presentation. Taken together, these results suggest that the functional failure of infected M phi to present exogenous Ag could be because either of interferences with the events leading to the meeting of la molecules with peptides derived from these exogenous Ag or to a competition for binding to la molecules between these peptides and parasite molecules.
Insights
Leishmania-infected macrophages show impaired antigen presentation to T cells. This dysfunction, observed in both infected and treated cells, suggests interference with antigen processing or competition for MHC molecules.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Macrophages (M phi) infected with Leishmania are investigated for their antigen-presenting capabilities.
- Leishmania-specific CD4+ T lymphocytes rely on antigen presentation by infected cells.
Purpose of the Study:
- To assess the antigen-presenting cell (APC) function of Leishmania-infected bone marrow-derived macrophages.
- To determine the ability of infected macrophages to stimulate Leishmania-specific CD4+ T-cell hybridomas.
Main Methods:
- Bone marrow-derived macrophages infected with Leishmania amazonensis amastigotes were used.
- T-cell hybridomas specific for bacteriophage lambda repressor cl protein, human chorionic gonadotropin, or OVA were employed.
- Antigen presentation capacity, MHC (la) molecule expression, and peptide binding were analyzed.
Main Results:
- Infected macrophages exhibited reduced capacity to present native antigens to most T-cell hybridomas.
- No significant differences in MHC (la) expression or peptide-binding ability were found between infected and uninfected macrophages.
- Both infected and cured macrophages, as well as those exposed to parasite components, showed impaired antigen presentation.
Conclusions:
- The functional failure in antigen presentation by Leishmania-infected macrophages is likely due to interference with MHC-peptide complex formation or competition for MHC binding.
- These findings suggest a novel mechanism of immune evasion by Leishmania parasites.