Cytosolic Localization of Listeria monocytogenes Triggers an Early IFN- gamma Response by CD8 super(+) T Cells That Correlates with Innate Resistance to Infection

• Published in: Journal of Immunology Vol. 177; no. 10; pp. 7146 - 7154
• Main Authors: D'Orazio, Sarah EF, Troese, Matthew J, Starnbach, Michael N
• Format: Journal Article
• Language: English
• Published: 01.11.2006
• Subjects: Escherichia coli; Listeria monocytogenes
• ISSN: 0022-1767; 1365-2567

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 CD44 super(high)CD8 super(+) 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 CD44 super(high)CD8 super(+) 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 super(+) 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 super(+) 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 super(+) T cell IFN- gamma response (BALB/c, A/J, and SJL). These data suggest that participation of memory CD8 super(+) T cells in the early immune response against L. monocytogenes correlates with innate host resistance to infection.