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Updated: Jul 26, 2025
Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites
Published on: March 16, 2018
Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen
Iris Baars1,2, Moritz Jaedtka3,4, Leon-Alexander Dewitz1,2
1Experimental Immunodynamics, Institute of Molecular and Clinical Immunology, Medical Faculty, and.
Abstract:
The virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes but also on release and transfer into new host cells. Such cell-to-cell transfer could represent a target for counteracting microbial pathogenesis. However, our understanding of the underlying cellular and molecular processes remains woefully insufficient. Using intravital 2-photon microscopy of caspase-3 activation in the Leishmania major-infected (L. major-infected) live skin, we showed increased apoptosis in cells infected by the parasite. Also, transfer of the parasite to new host cells occurred directly without a detectable extracellular state and was associated with concomitant uptake of cellular material from the original host cell. These in vivo findings were fully recapitulated in infections of isolated human phagocytes. Furthermore, we observed that high pathogen proliferation increased cell death in infected cells, and long-term residency within an infected host cell was only possible for slowly proliferating parasites. Our results therefore suggest that L. major drives its own dissemination to new phagocytes by inducing host cell death in a proliferation-dependent manner.
Insights
Leishmania major parasites spread to new host cells by causing infected cells to die, a process dependent on parasite proliferation. This direct cell-to-cell transfer avoids an extracellular stage, aiding pathogen dissemination.
Area of Science:
- Cell biology
- Immunology
- Parasitology
Background:
- Intracellular pathogens' virulence depends on surviving within host cells and transferring to new ones.
- Understanding the mechanisms of pathogen cell-to-cell transfer is crucial for developing countermeasures.
- Current knowledge of these processes is limited.
Purpose of the Study:
- To investigate the in vivo mechanisms of Leishmania major cell-to-cell transfer.
- To elucidate the role of host cell death in parasite dissemination.
- To explore the relationship between parasite proliferation and host cell survival.
Main Methods:
- Intravital 2-photon microscopy of caspase-3 activation in Leishmania major-infected live skin.
- Infection of isolated human phagocytes.
- Observation of parasite proliferation and host cell death.
Main Results:
- Leishmania major infection induces apoptosis (programmed cell death) in infected host cells.
- Parasite transfer occurs directly from infected to new host cells, without an extracellular phase.
- High parasite proliferation correlates with increased host cell death; slow proliferation allows longer host cell residency.
- Infected cells transfer cellular material during parasite transfer.
Conclusions:
- Leishmania major actively promotes its dissemination by inducing host cell death in a proliferation-dependent manner.
- Direct cell-to-cell transfer is a key mechanism for Leishmania major spread.
- Parasite proliferation rate critically influences host cell survival and parasite dissemination strategy.
