Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

Autor:	Brown AF; Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Murphy AG; Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Lalor SJ; Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Leech JM; Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., O'Keeffe KM; Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Mac Aogáin M; Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin, Ireland., O'Halloran DP; Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland., Lacey KA; Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Tavakol M; Department of Medical Microbiology & Infectious Diseases, Erasmus Medical Center, Rotterdam, Netherlands., Hearnden CH; Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Fitzgerald-Hughes D; Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland., Humphreys H; Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland.; Department of Microbiology, Beaumont Hospital, Dublin, Ireland., Fennell JP; Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin, Ireland.; Department of Clinical Microbiology, Adelaide Meath & National Children's Hospital, Dublin, Ireland., van Wamel WJ; Department of Medical Microbiology & Infectious Diseases, Erasmus Medical Center, Rotterdam, Netherlands., Foster TJ; Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland., Geoghegan JA; Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland., Lavelle EC; Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.; Advanced Materials and Bioengineering Research Centre (AMBER), Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin, Ireland., Rogers TR; Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin, Ireland.; Department of Clinical Microbiology, St. James's Hospital, Dublin, Ireland., McLoughlin RM; Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Jazyk:	angličtina
Zdroj:	PLoS pathogens [PLoS Pathog] 2015 Nov 05; Vol. 11 (11), pp. e1005226. Date of Electronic Publication: 2015 Nov 05 (Print Publication: 2015).
DOI:	10.1371/journal.ppat.1005226
Abstrakt:	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:	MEDLINE
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