Related Experiment Video

Updated: Jun 6, 2026

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
09:51

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

Published on: July 26, 2017

SR-A/MARCO-mediated ligand delivery enhances intracellular TLR and NLR function, but ligand scavenging from cell

Subhankar Mukhopadhyay1, Audrey Varin, Yunying Chen

  • 1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, United Kingdom.

Blood
|November 25, 2010
PubMed

Insights

Scavenger receptors SR-A and MARCO control inflammation by internalizing ligands. This process dampens surface Toll-like receptor 4 (TLR4) responses while boosting intracellular TLR3, NOD2, and NALP3 activation.

Area of Science:

  • Immunology
  • Innate Immunity
  • Receptor Signaling

Background:

  • Phagocytic receptors like scavenger receptor A (SR-A) and MARCO are crucial for particle uptake but don't initiate inflammation alone.
  • The interplay between phagocytic receptors and inflammatory sensors remains poorly understood.
  • SR-A and MARCO are implicated in inflammatory disorders, yet their precise role is unclear.

Purpose of the Study:

  • To investigate how scavenger receptors SR-A and MARCO influence innate immune responses.
  • To determine the combined effects of SR-A/MARCO ligation with Toll-like receptors (TLRs) and NOD-like receptors (NLRs).
  • To elucidate the mechanism by which SR-A and MARCO modulate inflammatory signaling pathways.

Main Methods:

  • Utilized knockout mice lacking SR-A, MARCO, or both.
  • Employed various polyanionic ligands to stimulate SR-A/MARCO and selected TLRs (TLR4, TLR3) and NLRs (NOD2, NALP3).
  • Assessed inflammatory responses following combinatorial receptor activation.

Main Results:

  • SR-A and MARCO attenuated TLR4-mediated inflammatory responses.
  • These scavenger receptors enhanced responses mediated by intracellular TLR3, NOD2, and NALP3.
  • Ligand internalization by SR-A/MARCO prevented surface TLR sensing while increasing intracellular availability.

Conclusions:

  • SR-A and MARCO act as regulators of innate immunity by modulating inflammatory signaling.
  • The internalization activity of SR-A/MARCO redirects ligand sensing from surface to intracellular receptors.
  • This mechanism highlights a novel way phagocytic receptors shape innate immune responses and inflammation.

More Related Videos

Fluorescence Assays for the Study of Mycobacterium tuberculosis Interaction with the Immune Receptor SLAMF107:42

Fluorescence Assays for the Study of Mycobacterium tuberculosis Interaction with the Immune Receptor SLAMF1

Published on: February 28, 2025

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

Related Concept Videos

Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Types of Signaling Molecules01:32

Types of Signaling Molecules

In multicellular organisms, many molecules transmit signals between cells to pass information. These signals vary in complexity and include small peptides, nucleotides, steroids, fatty acid derivatives, and dissolved gases such as nitric oxide. Some signaling molecules diffuse through the plasma membrane to act locally between neighboring cells or travel long distances. Others remain attached to the cell surface, transmitting information to other cells only when they make contact. In some...
Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...