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Acquired macrophage resistance to in vitro infection with Leishmania
Abstract:
An important feature of pathogenesis in leishmaniasis is the ability of the intracellular amastigote to gain entry into host mononuclear phagocytes and subsequently replicate. Resident peritoneal macrophages freshly harvested from Leishmania tropica-infected C57B1/6 mice and uninfected controls were therefore compared for their ability to ingest L tropica amastigotes in vitro. Macrophages from infected mice had a strikingly reduced ability to ingest parasites, but they ingested latex beads and IgG-sensitized erythrocytes as well as or more than control macrophages. Preincubation of these macrophages for 24 hr restored the degree of parasite ingestion to control levels. This alteration in macrophage function could be observed as early as two weeks of infection and persisted until spontaneous resolution of the infection occurred at about six weeks. The observations suggest that acquired defense in leishmaniasis may include a specific inhibition of amastigote uptake by host macrophages.
Insights
In leishmaniasis, macrophages from infected mice show reduced parasite uptake. This specific inhibition of Leishmania tropica amastigote entry by host macrophages may be part of the acquired immune defense.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Leishmaniasis pathogenesis involves intracellular amastigote replication within host mononuclear phagocytes.
- Understanding macrophage interactions is crucial for developing effective leishmaniasis treatments.
Purpose of the Study:
- To investigate the phagocytic capacity of macrophages from Leishmania tropica-infected mice for amastigotes.
- To determine if infection alters macrophage uptake of parasites specifically.
Main Methods:
- Resident peritoneal macrophages were harvested from Leishmania tropica-infected and control C57B1/6 mice.
- Macrophage phagocytosis of L. tropica amastigotes, latex beads, and IgG-sensitized erythrocytes was assessed in vitro.
- The effect of 24-hour preincubation on macrophage phagocytic function was evaluated.
Main Results:
- Macrophages from infected mice exhibited significantly reduced ability to ingest L. tropica amastigotes compared to controls.
- Phagocytosis of latex beads and opsonized erythrocytes by infected macrophages was comparable to or greater than control macrophages.
- Restoration of normal parasite ingestion levels was observed after 24-hour preincubation of infected macrophages.
- This impaired phagocytosis was evident from two weeks post-infection and persisted until spontaneous resolution.
Conclusions:
- Leishmania tropica infection specifically inhibits the uptake of amastigotes by host macrophages.
- This functional alteration in macrophages suggests a role in the host's acquired defense mechanisms against leishmaniasis.
- The findings highlight a potential target for therapeutic interventions aimed at enhancing macrophage clearance of parasites.