Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function

Area of Science:

• Cardiology
• Infectious Diseases
• Microbiology

Background:

• Invasive pneumococcal disease (IPD) in the elderly often leads to adverse cardiac events, including heart failure and arrhythmias.
• The mechanisms linking Streptococcus pneumoniae infection to cardiac complications are not fully understood.

Purpose of the Study:

• To identify and characterize previously unrecognized microscopic cardiac lesions (microlesions) in the myocardium during bacteremic pneumococcal infection.
• To investigate the role of pneumococcal components and host factors in microlesion formation and potential cardiac damage.

Main Methods:

• Microscopic examination of cardiac tissue from infected mice, non-human primates, and humans.
• Assessment of cardiac function markers (serum troponin, electrophysiology) in mice.
• Analysis of bacterial translocation mechanisms and immune responses.
• Evaluation of protective strategies using immunization.

Main Results:

• Microlesions were identified in the myocardium of mice, macaques, and humans during IPD.
• In mice, IPD severity correlated with cardiac damage markers and microlesion development.
• Pneumolysin toxin was essential for microlesion formation; Interleukin-1β was absent.
• Antibiotic treatment led to lesion maturation with immune cell infiltration and collagen deposition.
• Bacterial translocation involved pneumococcal adhesin CbpA and host receptors (LR, PAFR).
• Immunization with CbpA-based constructs protected mice against microlesion formation.

Conclusions:

• Microlesion formation in the heart is a novel finding during invasive pneumococcal disease.
• These microlesions, driven by pneumolysin, may contribute to acute and chronic cardiac dysfunction observed in IPD patients.
• Targeting bacterial factors like CbpA or host receptors involved in translocation offers a potential avenue for preventing IPD-associated cardiac damage.