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Updated: Jul 7, 2025
Investigating the Phagocytosis of Leishmania using Confocal Microscopy
Published on: July 29, 2021
Leishmania donovani mevalonate kinase regulates host actin for inducing phagocytosis
Tanvir Bamra1, Taj Shafi1, Sushmita Das2
1Department of Molecular Biology, ICMR- Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, 800 007, India.
Abstract:
Despite the well-established role of macrophages in phagocytosing Leishmania, the contribution of the parasite to this process is not well understood. Present study provides insights into the mechanism underlying the MVK-induced entry of L. donovani and improve our knowledge of host-pathogen interactions. We have discussed Mevalonate kinase (MVK)-induced actin reorganization, modulation of signaling pathways and host cell functions. Our results show that LdMVK gains access to macrophage cytosol and induces actin assembly modulation through the activation of actin-related proteins: VASP, Src and ERM. We have also demonstrated that LdMVK induces Ca2+ signaling and Akt pathway in macrophages, which are critical components of Leishmania survival and proliferation. Interestingly, we found that antibodies against LdMVK can kill Leishmania-infected macrophages in culture by forming extracellular traps, highlighting the potential of LdMVK in inhibiting parasite death. Overall, LdMVK is a virulent factor in Leishmania that mediates parasite internalization and host modulation by targeting host proteins phosphorylation and calcium homeostasis having significant implications in disease progression.
Insights
Leishmania donovani uses Mevalonate kinase (MVK) to enter host macrophages, manipulating actin and signaling pathways for survival. Antibodies targeting LdMVK show potential for treating leishmaniasis.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- Macrophages are key in Leishmania infection, but parasite-driven invasion mechanisms are unclear.
- Understanding host-pathogen interactions is crucial for developing anti-Leishmania strategies.
Purpose of the Study:
- To elucidate the role of Leishmania donovani Mevalonate kinase (LdMVK) in parasite entry and host cell manipulation.
- To investigate LdMVK's impact on actin reorganization, signaling pathways, and macrophage functions.
Main Methods:
- Analysis of LdMVK's interaction with host cell machinery.
- Investigating modulation of actin-related proteins (VASP, Src, ERM).
- Assessing effects on calcium (Ca2+) signaling and the Akt pathway.
Main Results:
- LdMVK enters the macrophage cytosol, inducing actin assembly modulation via VASP, Src, and ERM activation.
- LdMVK triggers Ca2+ signaling and Akt pathway activation in macrophages.
- Antibodies against LdMVK induce extracellular trap formation, killing infected macrophages.
Conclusions:
- LdMVK is a virulence factor mediating Leishmania internalization and host cell modulation.
- LdMVK targets host protein phosphorylation and calcium homeostasis, impacting disease progression.
- LdMVK presents a potential target for therapeutic intervention against leishmaniasis.
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