10779/rcsi.10768154.v1
Aisling F. Brown
Aisling F.
Brown
Alison G. Murphy
Alison G.
Murphy
Stephen J. Lalor
Stephen J.
Lalor
John M. Leech
John M.
Leech
Kate M. O'Keeffe
Kate M.
O'Keeffe
Micheál Mac Aogáin
Micheál Mac
Aogáin
Dara P. O'Halloran
Dara P.
O'Halloran
Keenan A. Lacey
Keenan A.
Lacey
Mehri Tavakol
Mehri
Tavakol
Claire H. Hearnden
Claire H.
Hearnden
Deirdre Fitzgerald-Hughes
Deirdre
Fitzgerald-Hughes
Hilary Humphreys
Hilary
Humphreys
Jérôme P. Fennell
Jérôme P.
Fennell
Willem J. van Wamel
Willem J.
van Wamel
Timothy J. Foster
Timothy J.
Foster
Joan A. Geoghegan
Joan A.
Geoghegan
Ed C. Lavelle
Ed C.
Lavelle
Thomas R. Rogers
Thomas R.
Rogers
Rachel M. McLoughlin
Rachel M.
McLoughlin
Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.
Royal College of Surgeons in Ireland
2019
Adjuvants
Immunologic
Adoptive Transfer
Adult
Aged
Animals
Antigens
Female
Humans
Immunologic Memory
Interleukin-17
Male
Mice
Inbred C57BL
Knockout
Middle Aged
Staphylococcal Infections
Staphylococcal Skin Infections
Staphylococcus aureus
Th1 Cells
Clinical Microbiology
2019-11-22 15:19:12
Journal contribution
https://repository.rcsi.com/articles/journal_contribution/Memory_Th1_Cells_Are_Protective_in_Invasive_Staphylococcus_aureus_Infection_/10768154
<p>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.</p>