Sex differences in a murine model of infective endocarditis

Area of Science:

• Cardiovascular Disease
• Infectious Disease Immunology
• Sex Differences in Disease

Background:

• Infective endocarditis (IE) is a severe infection of the heart valves with higher mortality in males.
• The biological mechanisms underlying this male predominance in IE are not well understood.

Purpose of the Study:

• To investigate the sex-specific differences in immune response and disease severity in a murine model of infective endocarditis.
• To establish a reliable murine model for studying the sex disparity in IE.

Main Methods:

• Induction of IE in C57BL6 mice via wire-induced aortic valve injury followed by Staphylococcus aureus injection.
• Assessment of bacterial load, cardiac function (echocardiography), systemic cytokine levels, and immune cell infiltration (flow cytometry, immunofluorescence).

Main Results:

• Male mice exhibited higher bacterial loads, increased valve damage, and more severe cardiac dysfunction.
• Males showed elevated systemic inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α).
• Females demonstrated enhanced early recruitment of macrophages and neutrophils to the infected valve, correlating with reduced bacterial burden.

Conclusions:

• The murine IE model recapitulates the clinical sex disparity, with males experiencing more severe disease.
• Females mount a more effective, localized immune response, conferring protection against severe IE.
• This model provides a platform for exploring molecular factors driving sex-specific IE susceptibility.