Macrophage polarization during Streptococcus agalactiae infection is isolate specific

Larisa Janžič1, Jernej Repas2, Mojca Pavlin2,3

  • 1Department of Cell Immunology, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Abstract

Insights

Group B Streptococcus (GBS) isolates vary in their ability to cause invasive infections. Colonizing GBS strains are more cytotoxic, while invasive strains evade immune responses by exploiting macrophages.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • * Streptococcus agalactiae* (Group B *Streptococcus*, GBS) is a significant cause of neonatal infections, including sepsis, meningitis, and pneumonia.
  • * While intrapartum antibiotic prophylaxis reduces early-onset disease, effective prevention of late-onset disease and infections in immunocompromised individuals remains a challenge.
  • * Further research into GBS pathogenesis and host-pathogen interactions is crucial.

Purpose of the Study:

  • * To investigate the impact of different GBS isolates on macrophage immune responses.
  • * To analyze isolate-specific differences in phagocytosis, immune cell activation, metabolism, and cytotoxicity.
  • * To understand how GBS serotypes and origins (colonizing vs. invasive) influence host immune evasion.

Main Methods:

  • * Genotyped 12 GBS isolates from various serotypes and sequence types.
  • * Assessed macrophage phagocytic uptake using flow cytometry.
  • * Measured co-stimulatory molecule (CD80, CD86) and scavenger receptor expression.
  • * Analyzed macrophage glycolysis and mitochondrial respiration in real-time.
  • * Quantified GBS-mediated cytotoxicity via LDH release and real-time microscopy.

Main Results:

  • * Significant isolate-specific variations in phagocytic uptake, with serotype III isolates showing over 70% uptake and serotype Ib isolates showing 10%.
  • * Colonizing GBS isolates induced higher CD80/CD86 expression compared to invasive isolates.
  • * GBS infection enhanced macrophage glycolysis and mitochondrial respiration, with serotype III isolates being potent activators.
  • * Macrophages exhibited differential resistance to GBS cytotoxicity, with vaginal isolates being more cytotoxic than blood isolates.

Conclusions:

  • * GBS isolates exhibit distinct potentials for invasiveness versus colonization.
  • * Colonizing GBS isolates demonstrate higher cytotoxicity, potentially contributing to their clearance.
  • * Invasive GBS isolates appear adept at exploiting macrophages, facilitating immune evasion and antibiotic resistance.