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Updated: Dec 17, 2025
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Targeting leukocidin-mediated immune evasion protects mice from Staphylococcus aureus bacteremia
Kayan Tam1, Keenan A Lacey1, Joseph C Devlin1
1Department of Microbiology, New York University Grossman School of Medicine, New York, NY.
Abstract:
Staphylococcus aureus is responsible for various diseases in humans, and recurrent infections are commonly observed. S. aureus produces an array of bicomponent pore-forming toxins that target and kill leukocytes, known collectively as the leukocidins. The contribution of these leukocidins to impair the development of anti-S. aureus adaptive immunity and facilitate reinfection is unclear. Using a murine model of recurrent bacteremia, we demonstrate that infection with a leukocidin mutant results in increased levels of anti-S. aureus antibodies compared with mice infected with the WT parental strain, indicating that leukocidins negatively impact the generation of anti-S. aureus antibodies in vivo. We hypothesized that neutralizing leukocidin-mediated immune subversion by vaccination may shift this host-pathogen interaction in favor of the host. Leukocidin-immunized mice produce potent leukocidin-neutralizing antibodies and robust Th1 and Th17 responses, which collectively protect against bloodstream infections. Altogether, these results demonstrate that blocking leukocidin-mediated immune evasion can promote host protection against S. aureus bloodstream infection.
Insights
Staphylococcus aureus leukocidins hinder antibody generation, promoting recurrent infections. Vaccination against these toxins enhances anti-S. aureus immunity and protects against bloodstream infections.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Staphylococcus aureus causes recurrent human infections.
- Leukocidins, toxins produced by S. aureus, target and kill leukocytes.
- The role of leukocidins in hindering adaptive immunity and facilitating reinfection is not well understood.
Purpose of the Study:
- To investigate the impact of leukocidins on anti-S. aureus antibody generation.
- To determine if neutralizing leukocidin-mediated immune subversion through vaccination can improve host defense against S. aureus infections.
Main Methods:
- A murine model of recurrent bacteremia was utilized.
- Mice were infected with wild-type (WT) S. aureus and a leukocidin mutant.
- Immune responses, including antibody levels and Th1/Th17 responses, were analyzed in leukocidin-immunized mice.
Main Results:
- Infection with a leukocidin mutant led to higher anti-S. aureus antibody levels compared to WT infection.
- Leukocidin immunization induced potent neutralizing antibodies and robust Th1 and Th17 responses.
- Vaccination against leukocidins protected mice against S. aureus bloodstream infections.
Conclusions:
- S. aureus leukocidins negatively impact the generation of anti-S. aureus antibodies in vivo.
- Blocking leukocidin-mediated immune evasion via vaccination promotes host protection.
- Targeting leukocidins represents a potential strategy to combat S. aureus infections.
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