Related Experiment Videos
Presentation of the protective parasite antigen LACK by Leishmania-infected macrophages
E Prina1, T Lang, N Glaichenhaus
1Unit of Cellular Immunophysiology, Pasteur Institute, Paris, France.
Abstract:
Macrophages are apparently the only cells that in vivo allow the growth of the intracellular pathogen Leishmania. They are thus generally considered as likely candidates for the presentation of parasite Ag to CD4+ T lymphocytes known to be involved in protective and counterprotective immune responses. In the present study, we examined whether mouse macrophages infected with Leishmania were capable of stimulating T cell hybrids and a T cell clone reacting with the previously identified protective Ag LACK (Leishmania homologue of receptors for Activated C Kinase). This parasite protein is expressed in both promastigote and amastigote stages of Leishmania. We found that IFN-gamma-treated macrophages recently infected with live Leishmania promastigotes were fully competent to activate LACK-reactive T cells. However, at later times of infection, permissive macrophages infected with promastigotes were no longer able to present LACK, in spite of the presence of numerous intracellular parasites. This punctual presentation of LACK was apparently linked with the destruction, at least partial, of the intracellular parasites. In contrast, macrophages infected with live Leishmania amastigotes were always unable to stimulate the LACK-specific T cells. Amastigote-infected macrophages could, however, reactivate the T cells if LACK-delta(1), a recombinant form of LACK, was added as an exogenous protein in the culture medium. Similar results were obtained with all combinations tested involving macrophages from various origins, different activating cytokines (IFN-gamma, granulocyte-macrophage CSF, IL-4), several Leishmania species (L. amazonensis, L. major, L. donovani), and 15 different LACK-reactive T cell hybrids and clones. From these data, it is tempting to propose that the differentiation of promastigotes into amastigotes, which leads to a better survival of the parasites within macrophages, also allows them to go unnoticed by the immune system.
Insights
Macrophages present Leishmania antigens to T cells, but this ability is stage-dependent. Early Leishmania promastigote infections allow antigen presentation, while later stages and amastigote forms evade immune detection.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Macrophages are key host cells for Leishmania intracellular survival.
- Macrophages present parasite antigens to CD4+ T lymphocytes, crucial for immune responses.
- Leishmania homologue of receptors for Activated C Kinase (LACK) is a protective antigen expressed in Leishmania.
Purpose of the Study:
- To investigate the capacity of Leishmania-infected macrophages to stimulate LACK-specific T cells.
- To determine how parasite stage and infection duration affect antigen presentation by macrophages.
Main Methods:
- Infection of mouse macrophages with Leishmania promastigotes and amastigotes.
- Co-culture of infected macrophages with LACK-reactive T cell hybrids and clones.
- Assessment of T cell activation in response to parasite antigen presentation.
Main Results:
- IFN-gamma-treated macrophages infected with early Leishmania promastigotes effectively presented LACK antigen.
- Later-stage promastigote infections and all amastigote infections rendered macrophages unable to present LACK.
- Exogenous recombinant LACK could reactivate T cells from amastigote-infected macrophages.
Conclusions:
- Leishmania parasites modulate macrophage antigen presentation capabilities.
- The differentiation into amastigotes may facilitate parasite evasion of the immune system by downregulating LACK presentation.
- Macrophage antigen presentation is critical for T cell-mediated immunity against Leishmania.