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Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major

Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major

Published on: October 28, 2022

Using machine learning to dissect host kinases required for Leishmania internalization and development.

Ling Wei¹, Umaru Barrie², Gina M Aloisio²

¹Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, United States.

Molecular and Biochemical Parasitology

|August 24, 2024

Summary

This summary is machine-generated.

Researchers identified host kinases regulating Leishmania parasite uptake and survival in macrophages. This study reveals novel kinases and emphasizes the complex kinase networks involved in host-pathogen interactions during infection.

Keywords:

Complement receptor Fc receptor Kinase regression Leishmania Phagocytosis Phosphosignaling

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Published on: March 16, 2018

Area of Science:

Host-pathogen interactions
Cellular biology
Immunology

Background:

Leishmania parasites infect mammals, cycling between sandflies and host phagocytes.
Parasite uptake by phagocytes and survival within macrophages are critical for disease establishment.
Host kinases play a role in regulating these processes.

Purpose of the Study:

To identify host kinase regulators of Leishmania promastigote and amastigote uptake by macrophages.
To uncover kinases involved in parasite survival within host cells.
To differentiate parasite-specific uptake mechanisms from general phagocytosis.

Main Methods:

An image-based kinase regression screen using 38 kinase inhibitors.
Targeted inert beads coated with complement/C3bi or IgG as controls.
Analysis of kinase roles in receptor-mediated phagocytosis and parasite internalization.

Main Results:

Identified known kinases (Src family kinases, Abl family kinases, SYK) and novel kinases regulating Leishmania uptake.
Predicted host kinases essential for promastigote-to-amastigote conversion and amastigote survival.
Found kinases that preferentially regulate parasite uptake over bead uptake.

Conclusions:

Multiple interconnected host kinase networks are required for Leishmania infection.
Kinases involved in parasite life cycle stages can differ based on receptor binding and life cycle stage.
Host kinase regulation of Leishmania internalization may involve mechanisms distinct from generalized phagocytosis.