Related Experiment Video

Updated: Feb 13, 2026

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation
09:04

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation

Published on: September 7, 2010

12.0K

Mannose receptor (MR) and Toll-like receptor 2 (TLR2) influence phagosome maturation during Leishmania infection

R E Polando1, B C Jones1, C Ricardo1

  • 1Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, USA.

Parasite Immunology
|March 8, 2018
PubMed

Insights

Leishmania parasites delay macrophage phagosome maturation via mannose receptor (MR) and Toll-like receptor 2 (TLR2) interactions. Blocking these receptors accelerates phagosome maturation, impacting parasite survival.

Area of Science:

  • Immunology
  • Cell Biology
  • Infectious Diseases

Background:

  • Leishmania parasites infect macrophages via receptor-mediated phagocytosis.
  • Leishmania survive within the phagolysosome, suggesting mechanisms to evade host defenses.
  • Phagosome maturation is a critical step in controlling intracellular pathogens.

Purpose of the Study:

  • To investigate the roles of mannose receptor (MR) and Toll-like receptor 2 (TLR2) in Leishmania phagosome maturation.
  • To understand how Leishmania manipulates phagosome maturation for survival.
  • To elucidate the signaling pathways involved in Leishmania-macrophage interactions.

Main Methods:

  • Utilized wild-type (WT) and knockout (MR-/-, MyD88-/-, TLR2-/-) macrophages.
  • Infected macrophages with Leishmania major and Leishmania donovani.
  • Monitored phagosome maturation using LAMP1 and EEA1 markers.
  • Assessed the role of Leishmania lipophosphoglycan (LPG) and serum opsonization.

Main Results:

  • Leishmania delayed phagosome maturation in WT macrophages, reaching LAMP1 positivity at 6 hours.
  • MR-/- macrophages showed accelerated early maturation (LAMP1 positive by ~2 hours), with transient LAMP1 loss and EEA1 gain.
  • Leishmania LPG was essential for maturation delay in WT and MR-/- cells.
  • Absence of MyD88 or TLR2 led to significantly faster phagosome maturation (~1-2 hours LAMP1 positive).
  • Serum opsonization normalized maturation in MR-/- macrophages.

Conclusions:

  • Phagosome maturation is modulated by complex receptor-ligand interactions, including MR and TLR2.
  • Leishmania utilizes specific molecules like LPG to interfere with phagosome maturation.
  • MyD88 and TLR2 signaling pathways are crucial for Leishmania's ability to delay phagosome maturation.
  • Targeting these host-pathogen interactions could offer new therapeutic strategies against Leishmaniasis.
Keywords:
Leishmaniamacrophagepattern recognitionphagosome maturationreceptor

More Related Videos

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling09:51

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling

Published on: July 26, 2017

13.0K
A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces07:55

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces

Published on: January 7, 2020

7.9K

Related Concept Videos

Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.7K
Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
111.5K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
86.8K
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
132.2K
Types of Receptors: Internal Receptors01:07

Types of Receptors: Internal Receptors

Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
32.7K
Types of Receptors: Cell Surface Receptors01:28

Types of Receptors: Cell Surface Receptors

Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored (integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, converting an extracellular signal into an intracellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are...
27.7K