Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells.

Area of Science:

• Immunology
• Microbiology
• Vaccinology

Background:

• Staphylococcus aureus infections often lack long-lived protective immunity, a phenomenon not fully understood.
• Antibodies (Abs) are implicated in protection against recurrent infections, but S. aureus employs strategies to evade this response.
• Staphylococcus protein A (SpA) is a surface protein that influences B cell responses, promoting expansion and inducing cell death.

Purpose of the Study:

• To investigate the mechanism by which S. aureus infection fails to induce long-lived protective immunity in a murine model.
• To elucidate the role of Staphylococcus protein A (SpA) in modulating the B cell response and plasma cell fate.
• To determine the impact of SpA on the establishment of long-lived antibody titers and B cell memory.

Main Methods:

• A murine model was used to study the effects of wild-type and SpA-deficient S. aureus on B cell responses.
• Analysis focused on the fate of plasmablasts and plasma cells (PCs) in the bone marrow (BM).
• Antibody titers and B cell memory formation were assessed during primary and secondary immune responses.

Main Results:

• SpA altered the fate of plasmablasts and PCs, favoring short-lived responses and reducing long-lived, bone marrow-resident PCs.
• The absence of long-lived PCs led to a rapid decline in antigen-specific, class-switched antibodies.
• Mice challenged with SpA-deficient S. aureus maintained long-term antibody titers due to sustained proliferation of PCs in BM niches.
• SpA's effects were specific to the secondary response; primary responses and B cell memory formation were unaffected.

Conclusions:

• The failure to establish long-term protective antibody titers against S. aureus is not due to impaired B cell memory formation.
• Staphylococcus protein A (SpA) actively reduces the proliferative capacity of plasma cells entering the bone marrow.
• SpA diminishes the pool of long-lived plasma cells, thereby compromising sustained antibody production and long-term immunity.