Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.
Authors
Brown, Aisling FMurphy, 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
McLoughlin, Rachel M
Issue Date
2015Keywords
METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUSIMMUNE SYSTEM
MeSH
Adjuvants, ImmunologicAdoptive Transfer
Adult
Aged
Animals
Antigens
Female
Humans
Immunologic Memory
Interleukin-17
Male
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Staphylococcal Infections
Staphylococcal Skin Infections
Staphylococcus aureus
Th1 Cells
Metadata
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Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection. 2015, 11 (11):e1005226 PLoS Pathog.Journal
PLoS pathogensDOI
10.1371/journal.ppat.1005226PubMed ID
26539822Abstract
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.Item Type
ArticleLanguage
enISSN
1553-7374ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1005226
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