AUTHOR=Braverman Jessica , Monk Ian R. , Zhang Heran , Stinear Timothy P. , Wakim Linda M. 

TITLE=Polyclonal but not monoclonal circulating memory CD4+ T cells attenuate the severity of Staphylococcus aureus bacteremia

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1417220

DOI=10.3389/fimmu.2024.1417220

ISSN=1664-3224

ABSTRACT=<p><italic>Staphylococcus aureus</italic> bacteremia causes significant morbidity and mortality. Treatment of staphylococcal infections is hindered by widespread antibiotic resistance, and attempts to develop an <italic>S. aureus</italic> vaccine have failed. Improved <italic>S. aureus</italic> treatment and infection prevention options require a deeper understanding of the correlates of protective immunity. CD4<sup>+</sup> T cells have been identified as key orchestrators in the defense against <italic>S. aureus</italic>, but uncertainties persist regarding the subset, polarity, and breadth of the memory CD4<sup>+</sup> T-cell pool required for protection. Here, using a mouse model of systemic <italic>S. aureus</italic> infection, we discovered that the breadth of bacterium-specific memory CD4<sup>+</sup> T-cell pool is a critical factor for protective immunity against invasive <italic>S. aureus</italic> infections. Seeding mice with a monoclonal bacterium-specific circulating memory CD4<sup>+</sup> T-cell population failed to protect against systemic <italic>S. aureus</italic> infection; however, the introduction of a polyclonal and polyfunctional memory CD4<sup>+</sup> T-cell pool significantly reduced the bacterial burden. Our findings support the development of a multi-epitope T-cell-based <italic>S. aureus</italic> vaccine, as a strategy to mitigate the severity of <italic>S. aureus</italic> bacteremia.</p>