Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

Autor: 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
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: PLoS Pathogens, Vol 11, Iss 11, p e1005226 (2015)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1005226
Popis: 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.
Databáze: Directory of Open Access Journals
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