title: Cytosolic localization of Listeria monocytogenes triggers an early IFN-gamma response by CD8+ T cells that correlates with innate resistance to infection.
abstract: IFN-gamma is critical for innate immunity against Listeria monocytogenes (L. monocytogenes), and it has long been thought that NK cells are the major source of IFN-gamma during the first few days of infection. However, it was recently shown that a significant number of CD44highCD8+ T cells also secrete IFN-gamma in an Ag-independent fashion within 16 h of infection with L. monocytogenes. In this report, we showed that infection with other intracellular pathogens did not trigger this early IFN-gamma response and that cytosolic localization of Listeria was required to induce rapid IFN-gamma production by CD44highCD8+ T cells. Infection of C57BL/6 mice with an Escherichia coli strain expressing listeriolysin O (LLO), a pore-forming toxin from L. monocytogenes, also resulted in rapid IFN-gamma expression by CD8+ T cells. These results suggest that LLO expression is essential for induction of the early IFN-gamma response, although it is not yet clear whether LLO plays a direct role in triggering a signal cascade that leads to cytokine production or whether it is required simply to release other bacterial product(s) into the host cell cytosol. Interestingly, mouse strains that displayed a rapid CD8+ T cell IFN-gamma response (C57BL/6, 129, and NZB) all had lower bacterial burdens in the liver 3 days postinfection compared with mouse strains that did not have an early CD8+ T cell IFN-gamma response (BALB/c, A/J, and SJL). These data suggest that participation of memory CD8+ T cells in the early immune response against L. monocytogenes correlates with innate host resistance to infection.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA. sarah.dorazio@uky.edu
authors.forename: Sarah E F
authors.initials: SE
authors.lastname: D'Orazio
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Troese
authors.forename: Michael N
authors.initials: MN
authors.lastname: Starnbach
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D003600:Cytosol / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D013045:Species Specificity
chemical_list: D007371:Interferon-gamma