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

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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