Memory Th1 cells are protective in invasive Staphylococcus aureus infection

• Published in: PLoS Pathogens 2015
• Main Authors: Brown, Aisling F, Murphy, Alison G, Lalor, Stephen J, Leech, John M, O'Keeffe, Kate M, Aogain, Micheal Mac, O'Halloran, Dara P, Lacey, Keenan A, Tavakol, Mehri, Hearnden, Claire H, Fitzgerald-Hughes, Deirdre, Humphreys, Hilary, Fennell, Jerome P, van Wamel, Willem J, Foster, Timothy J, Geoghegan, Joan A, Lavelle, Ed. C, Rogers, Thomas R, McLoughlin, Rachel M
• Format: Report
• Language: English
• Subjects: Care and treatment; Complications and side effects; Health aspects; Influence; Interferon; Staphylococcus aureus infections; Vaccines
• ISSN: 1553-7366
• DOI: 10.1371/journal.ppat.1005226

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 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.sup.+], 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.