Memory Th1 cells are protective in invasive staphylococcus aureus infection

Aisling F Brown, Alison G Murphy, Stephen J Lalor, John M Leech, Kate M O'Keeffe, Micheál Mac Aogáin, Dara P O'Halloran, Keenan A Lacey, Mehri Tavakol, Claire H Hearnden, Deirdre Fitzgerald-Hughes, Hilary Humphreys, Jérôme P Fennell, Willem J van Wamel, Timothy J Foster, Joan A Geoghegan, Ed C Lavelle, Thomas R Rogers, Rachel M McLoughlin

Research output: Contribution to journalArticlepeer-review

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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 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.

Original languageEnglish
Article numbere1005226
Number of pages32
JournalPLoS pathogens
Volume11
Issue number11
DOIs
Publication statusPublished - 5 Nov 2015

Keywords

  • Adjuvants, Immunologic/pharmacology
  • Adoptive Transfer
  • Adult
  • Aged
  • Animals
  • Antigens/immunology
  • Female
  • Humans
  • Immunologic Memory
  • Interleukin-17/metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Staphylococcal Infections/immunology
  • Staphylococcal Skin Infections/immunology
  • Staphylococcus aureus/immunology
  • Th1 Cells/drug effects

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