Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection: e1005226

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...

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Bibliographic Details
Published in:PLoS pathogens 2015-11, Vol.11 (11)
Main Authors: Brown, Aisling F, Murphy, Alison G, Lalor, Stephen J, Leech, John M, O'Keeffe, Kate M, Aogáin, Micheál Mac, O'Halloran, Dara P, Lacey, Keenan A, Tavakol, Mehri, Hearnden, Claire H, Fitzgerald-Hughes, Deirdre, Humphreys, Hilary, Fennell, Jérôme P, Wamel, Willem Jvan, Foster, Timothy J, Geoghegan, Joan A, Lavelle, Ed C, Rogers, Thomas R, McLoughlin, Rachel M
Format: Article
Language:English
Subjects:
Antigens
Bacterial infections
Bacteriology
Clinical trials
Experiments
Genetic diversity
Genomes
Immune system
Lymphocytes
Medical research
Mortality
Pathogens
Staphylococcus aureus
Staphylococcus infections
Vaccines
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Summary: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 IFN[gamma] 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.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1005226