Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection

AF Brown, AG Murphy, SJ Lalor, JM Leech, KM O'Keeffe, M Mac Aogain, DP O'Halloran, KA Lacey, Mehri Tavakol, CH Hearnden, D Fitzgerald-Hughes, H Humphreys, JP Fennell, WJ van Wamel, TJ Foster, JA Geoghegan, EC Lavelle, TR Rogers, RM McLoughlin

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Abstract

Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFN gamma responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naive mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO(+), indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.
Original languageUndefined/Unknown
JournalPLoS Pathogens (print)
Volume11
Issue number11
DOIs
Publication statusPublished - 2015

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