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Published on: October 25, 2017
Evasion of macrophage scavenger receptor A-mediated recognition by pathogenic streptococci
Thomas Areschoug1, Johan Waldemarsson, Siamon Gordon
1Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. thomas.areschoug@med.lu.se
Abstract:
PRR recognize conserved structures on pathogenic microbes and are important for the defense against invading microorganisms. However, accumulating evidence indicates that many pathogens have evolved mechanisms to avoid recognition by PRR. One type of PRR is the macrophage scavenger receptor A (SR-A), which has been shown to play an important role in recognition and non-opsonic phagocytosis of pathogenic bacteria. The bacterial ligands for SR-A have been suggested to be LPS or lipoteichoic acid. Here, we use murine bone marrow-derived macrophages to analyze the role of SR-A in non-opsonic phagocytosis of two major Gram-positive pathogens, Streptococcus agalactiae (group B streptococcus; GBS) and Streptococcus pyogenes. We show that the polysaccharide capsule of GBS and the surface M protein of S. pyogenes, two important virulence factors, prevent SR-A-mediated non-opsonic phagocytosis of streptococci. The sialic acid moiety of the GBS capsule was crucial for its ability to prevent recognition by SR-A. Moreover, we show that a ligand on GBS recognized by SR-A in the absence of capsule is the surface lipoprotein Blr. These findings represent the first example of a microbial strategy to prevent recognition by SR-A and suggest that bacterial surface proteins may be of importance as ligands for SR-A.
Insights
Pathogenic bacteria evade immune recognition by Pattern Recognition Receptors (PRRs). Streptococcus virulence factors like GBS capsule and M protein block macrophage scavenger receptor A (SR-A) recognition, impacting phagocytosis.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Pattern Recognition Receptors (PRRs) are crucial for detecting conserved microbial structures and initiating immune responses.
- Pathogenic microbes have evolved mechanisms to evade PRR recognition, hindering host defense.
- Macrophage Scavenger Receptor A (SR-A) is a PRR involved in recognizing and phagocytosing pathogenic bacteria, with LPS or lipoteichoic acid previously suggested as ligands.
Purpose of the Study:
- To investigate the role of SR-A in the non-opsonic phagocytosis of Gram-positive pathogens Streptococcus agalactiae (GBS) and Streptococcus pyogenes.
- To identify bacterial factors that mediate or evade SR-A recognition.
Main Methods:
- Utilized murine bone marrow-derived macrophages to study phagocytosis.
- Analyzed the impact of GBS polysaccharide capsule and S. pyogenes M protein on SR-A-mediated phagocytosis.
- Investigated the role of sialic acid in GBS capsule's interaction with SR-A.
- Identified SR-A ligands on GBS in the absence of its capsule.
Main Results:
- The polysaccharide capsule of GBS and the surface M protein of S. pyogenes effectively prevent SR-A-mediated non-opsonic phagocytosis of these streptococci.
- Sialic acid within the GBS capsule is critical for blocking SR-A recognition.
- In the absence of the capsule, the surface lipoprotein Blr on GBS acts as a ligand for SR-A.
Conclusions:
- Bacterial virulence factors, such as the GBS capsule and S. pyogenes M protein, represent strategies to evade recognition by SR-A.
- This study provides the first evidence of microbial mechanisms evolved to prevent SR-A-mediated recognition.
- Bacterial surface proteins, like Blr, may serve as important ligands for SR-A, highlighting their potential role in host-pathogen interactions.
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