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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Microbial Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1417220

Polyclonal, but not monoclonal circulating memory CD4 + T cells attenuate the severity of S. aureus bacteraemia

Provisionally accepted
Jessica Braverman Jessica Braverman Ian R. Monk Ian R. Monk Heran Zhang Heran Zhang Timothy P. Stinear Timothy P. Stinear Linda M. Wakim Linda M. Wakim *
  • The University of Melbourne, Parkville, Australia

The final, formatted version of the article will be published soon.

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

    Keywords: Staph aureus bacteremia, memory CD4 + T lymphocytes, polyclonal T cells, Tissue resident CD4+ T cells, Circulating memory T cell subsets

    Received: 14 Apr 2024; Accepted: 13 May 2024.

    Copyright: © 2024 Braverman, Monk, Zhang, Stinear and Wakim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Linda M. Wakim, The University of Melbourne, Parkville, Australia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.