Cytosolic Localization ofListeria monocytogenesTriggers an Early IFN-γ Response by CD8+ T Cells That Correlates with Innate Resistance to Infection

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Abstract
IFN-γ 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-γ during the first few days of infection. However, it was recently shown that a significant number of CD44highCD8+ T cells also secrete IFN-γ 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-γ response and that cytosolic localization of Listeria was required to induce rapid IFN-γ 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-γ expression by CD8+ T cells. These results suggest that LLO expression is essential for induction of the early IFN-γ 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-γ 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-γ 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.