Cytosolic localization of Listeria monocytogenes triggers an early IFN-gamma response by CD8+ T cells that correlates with innate resistance to infection

• Published in: The Journal of immunology (1950) Vol. 177; no. 10; pp. 7146 - 7154
• Main Authors: D'Orazio, Sarah E F, Troese, Matthew J, Starnbach, Michael N
• Format: Journal Article
• Language: English
• Published: United States 15.11.2006
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - microbiology; Cytosol - immunology; Cytosol - metabolism; Cytosol - microbiology; Disease Models, Animal; Genetic Predisposition to Disease; Immunity, Innate; Immunologic Memory; Interferon-gamma - biosynthesis; Listeria monocytogenes - immunology; Listeriosis - genetics; Listeriosis - immunology; Listeriosis - microbiology; Mice; Mice, Inbred A; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NZB; Species Specificity
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.177.10.7146

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.