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Role of macrophage complement and lectin-like receptors in binding Leishmania parasites to host macrophages
Abstract:
This paper reviews briefly work carried out in our laboratory on the relative roles of the macrophage plasma membrane receptor (CR3) for the cleaved third complement component (iC3b) and the mannosyl/fucosyl receptor (MFR) in binding, ingestion and respiratory burst (RB) response elicited by promastigotes versus amastigotes of Leishmania donovani. In the absence of serum soluble inhibitors (mannan, ribonuclease B) of the MFR cause a dose-dependent reduction in the numbers of promastigotes binding to murine resident peritoneal macrophages and in the proportion of bound parasites eliciting a RB response. For amastigotes no consistent reduction in binding in the presence of mannan is observed but the proportion of parasites eliciting a RB is reduced. Serum-independent binding and ingestion of promastigotes, which are good activators of the alternative complement pathway, is also inhibited by the anti-CR3 monoclonal antibody M1/70, by Fab anti-C3, and by an inhibitor of C3 fixation, sodium salicyl hydroxamate. For amastigotes, which are poor activators of the alternative pathway, a lesser effect is observed with all three inhibitors of CR3-mediated binding. The results obtained with these three independent inhibitors provide strong evidence that cleaved macrophage-derived C3 (iC3b), which can be visualised on the parasite surface in electron microscope sections following addition of anti-C3 antibody and a protein A-gold conjugate, mediates binding to CR3. Modulation experiments in which either CR3 or MFR are rendered inaccessible demonstrate that both receptors must be present on the segment of the macrophage membrane with which the parasite makes contact to mediate binding and ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study reveals that both the complement receptor 3 (CR3) and mannosyl/fucosyl receptor (MFR) on macrophages are crucial for Leishmania donovani binding and ingestion. Inhibiting these receptors impacts the parasite
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Leishmania donovani parasites interact with macrophages through specific cell surface receptors.
- The complement receptor 3 (CR3) and mannosyl/fucosyl receptor (MFR) are key macrophage receptors involved in pathogen recognition.
- Understanding these interactions is vital for developing strategies against leishmaniasis.
Purpose of the Study:
- To investigate the distinct roles of CR3 and MFR in macrophage interactions with Leishmania donovani promastigotes and amastigotes.
- To determine how these receptors influence parasite binding, ingestion, and the subsequent respiratory burst response.
Main Methods:
- Utilized specific inhibitors (mannan, ribonuclease B, anti-CR3 antibody M1/70, Fab anti-C3, sodium salicyl hydroxamate) to block MFR and CR3.
- Quantified parasite binding and assessed the respiratory burst response elicited by Leishmania.
- Employed electron microscopy to visualize complement component C3 deposition on parasite surfaces.
Main Results:
- MFR inhibition reduced promastigote binding and respiratory burst, while amastigote binding was less affected but respiratory burst was reduced.
- CR3-mediated binding of promastigotes was significantly inhibited by anti-CR3 antibodies and complement fixation inhibitors.
- Both CR3 and MFR are necessary for efficient binding and ingestion, indicating a cooperative role in macrophage-parasite interactions.
Conclusions:
- Cleaved complement component C3 (iC3b) on the parasite surface mediates binding to CR3.
- Both CR3 and MFR must be engaged on the macrophage membrane for effective parasite binding and ingestion.
- The findings highlight the complex interplay of macrophage receptors in controlling Leishmania infection.