1. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.
- Author
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Brown, Aisling F., Murphy, Alison G., Lalor, Stephen J., Leech, John M., O’Keeffe, Kate M., Mac Aogáin, Micheál, O’Halloran, Dara P., Lacey, Keenan A., Tavakol, Mehri, Hearnden, Claire H., Fitzgerald-Hughes, Deirdre, Humphreys, Hilary, Fennell, Jérôme P., van Wamel, Willem J., Foster, Timothy J., Geoghegan, Joan A., Lavelle, Ed C., Rogers, Thomas R., and McLoughlin, Rachel M.
- Subjects
STAPHYLOCOCCUS aureus infections ,STAPHYLOCOCCUS aureus ,T cells ,INTERFERONS ,ANTIGENS - 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 IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve 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. [ABSTRACT FROM AUTHOR]- Published
- 2015
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