[HTML][HTML] Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection

AF Brown, AG Murphy, SJ Lalor, JM Leech… - PLoS …, 2015 - journals.plos.org
AF Brown, AG Murphy, SJ Lalor, JM Leech, KM O'Keeffe, M Mac Aogáin, DP O'Halloran…
PLoS pathogens, 2015journals.plos.org
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 …
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.
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