title: Staphylococcus aureus infection of mice expands a population of memory γδ T cells that are protective against subsequent infection.
abstract: The development of vaccines against Staphylococcus aureus has consistently failed in clinical trials, likely due to inefficient induction of cellular immunity. T cell-derived IL-17 is one of the few known correlates of antistaphylococcoal immunity, conferring protection against S. aureus infections through its ability to promote phagocytic cell effector functions. A comprehensive understanding of the discrete T cell subsets critical for site-specific IL-17-mediated bacterial clearance will therefore be necessary to inform the development of vaccines that efficiently target cellular immunity. In this study, we have identified a population of CD44+ CD27- memory γδ T cells, expanded upon infection of C57BL/6 mice with S. aureus, which produce high levels of IL-17 and mediate enhanced bacterial clearance upon reinfection with the bacterium. These cells are comprised largely of the Vγ4+ subset and accumulate at the site of infection subsequent to an initial Vγ1.1+ and Vγ2+ T cell response. Moreover, these Vγ4+ T cells are retained in the peritoneum and draining mediastinal lymph nodes for a prolonged period following bacterial clearance. In contrast to its critical requirement for γδ T cell activation during the primary infection, IL-1 signaling was dispensable for activation and expansion of memory γδ T cells upon re-exposure to S. aureus. Our findings demonstrate that a γδ T cell memory response can be induced upon exposure to S. aureus, in a fashion analogous to that associated with classical αβ T cells, and suggest that induction of IL-17-expressing γδ T cells may be an important property of a protective vaccine against S. aureus.
authors.affiliation: Host Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Dublin 2, Ireland.
authors.forename: Alison G
authors.initials: AG
authors.lastname: Murphy
authors.forename: Kate M
authors.initials: KM
authors.lastname: O'Keeffe
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lalor
authors.forename: Belinda M
authors.initials: BM
authors.lastname: Maher
authors.forename: Kingston H G
authors.initials: KH
authors.lastname: Mills
authors.forename: Rachel M
authors.initials: RM
authors.lastname: McLoughlin
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010538:Peritonitis / Q000276:immunology / Q000382:microbiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D013211:Staphylococcus aureus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta