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Leishmania donovani infection enhances macrophage viability in the absence of exogenous growth factor
K J Moore1, S J Turco, G Matlashewski
1Institute of Parasitology, McGill University, Ste. Anne-de-Bellevue, Quebec, Canada.
Abstract:
Bone marrow-derived macrophages rapidly die in the absence of macrophage growth factor (M-CSF). However, as demonstrated here, bone marrow-derived macrophages infected with Leishmania donovani exhibit increased viability in the absence of exogenous growth factor. Forty-eight hours after inoculation with promastigotes or amastigotes, infected cell cultures contained 180 and 95% more cells, respectively, than control cultures. This effect was specific to Leishmania infection, as uptake of latex beads or avirulent promastigotes by macrophages did not enhance cell viability. L. donovani-infected macrophages also displayed increased phagocytic capacity, as compared with control macrophages and macrophages grown continuously in M-CSF-containing medium. Supernatants collected from infected cells elaborated a factor(s) that enhanced macrophage viability but did not stimulate macrophage DNA synthesis. This activity of L. donovani-infected cell-conditioned medium could be abrogated by preincubation of macrophages with cycloheximide before inoculation with the parasite, implying that macrophage protein synthesis is required for the elaboration of this factor(s).
Insights
Leishmania donovani infection enhances macrophage survival without growth factors. Infected macrophages show increased viability and phagocytic capacity, suggesting a parasite-induced survival mechanism.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Bone marrow-derived macrophages require macrophage colony-stimulating factor (M-CSF) for survival.
- Leishmania donovani is an intracellular parasite that infects macrophages.
Purpose of the Study:
- To investigate the effect of Leishmania donovani infection on macrophage viability and function.
- To identify mechanisms by which Leishmania donovani influences macrophage survival.
Main Methods:
- Bone marrow-derived macrophages were infected with Leishmania donovani (promastigotes and amastigotes).
- Macrophage viability and phagocytic capacity were assessed in the presence and absence of M-CSF.
- Conditioned media from infected macrophages were analyzed for factors affecting macrophage viability.
Main Results:
- Leishmania donovani infection significantly increased macrophage viability in the absence of M-CSF.
- Infected macrophages exhibited enhanced phagocytic capacity compared to controls.
- Conditioned media from infected cells contained a factor that promoted macrophage viability but not DNA synthesis.
- This survival-promoting activity required de novo macrophage protein synthesis.
Conclusions:
- Leishmania donovani infection confers resistance to apoptosis in macrophages, independent of exogenous growth factors.
- The parasite induces macrophages to produce factors that enhance their own survival and phagocytic function.
- This represents a novel host-parasite interaction crucial for Leishmania survival and pathogenesis.