Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.
AuthorsBrown, 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
Hearnden, Claire H
Fennell, Jérôme P
van Wamel, Willem J
Foster, Timothy J
Geoghegan, Joan A
Lavelle, Ed C
Rogers, Thomas R
McLoughlin, Rachel M
KeywordsMETHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS
Mice, Inbred C57BL
Staphylococcal Skin Infections
MetadataShow full item record
CitationMemory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection. 2015, 11 (11):e1005226 PLoS Pathog.
AbstractMechanisms 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.
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