title: Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.
abstract: 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.
authors.affiliation: Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Aisling F
authors.initials: AF
authors.lastname: Brown
authors.affiliation: Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Alison G
authors.initials: AG
authors.lastname: Murphy
authors.affiliation: Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lalor
authors.affiliation: Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: John M
authors.initials: JM
authors.lastname: Leech
authors.affiliation: Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Kate M
authors.initials: KM
authors.lastname: O'Keeffe
authors.affiliation: Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Micheál
authors.initials: M
authors.lastname: Mac Aogáin
authors.affiliation: Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Dara P
authors.initials: DP
authors.lastname: O'Halloran
authors.affiliation: Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Keenan A
authors.initials: KA
authors.lastname: Lacey
authors.affiliation: Department of Medical Microbiology & Infectious Diseases, Erasmus Medical Center, Rotterdam, Netherlands.
authors.forename: Mehri
authors.initials: M
authors.lastname: Tavakol
authors.affiliation: Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Claire H
authors.initials: CH
authors.lastname: Hearnden
authors.affiliation: Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Fitzgerald-Hughes
authors.affiliation: Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland.|Department of Microbiology, Beaumont Hospital, Dublin, Ireland.
authors.forename: Hilary
authors.initials: H
authors.lastname: Humphreys
authors.affiliation: Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin, Ireland.|Department of Clinical Microbiology, Adelaide Meath & National Children's Hospital, Dublin, Ireland.
authors.forename: Jérôme P
authors.initials: JP
authors.lastname: Fennell
authors.affiliation: Department of Medical Microbiology & Infectious Diseases, Erasmus Medical Center, Rotterdam, Netherlands.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van Wamel
authors.affiliation: Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Foster
authors.affiliation: Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Joan A
authors.initials: JA
authors.lastname: Geoghegan
authors.affiliation: 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.
authors.forename: Ed C
authors.initials: EC
authors.lastname: Lavelle
authors.affiliation: Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin, Ireland.|Department of Clinical Microbiology, St. James's Hospital, Dublin, Ireland.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Rogers
authors.affiliation: Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: McLoughlin
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D019264:Adoptive Transfer; D000328:Adult; D000368:Aged; D000818:Animals; D000941:Antigens / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000276:immunology*; D013207:Staphylococcal Skin Infections / Q000276:immunology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D020381:Interleukin-17