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Cytosolic Localization of Listeria monocytogenes Triggers an Early IFN- Response by CD8⁺ T Cells That Correlates with Innate Resistance to Infection¹

Sarah E. F. D’Orazio^2,*, Matthew J. Troese^* and Michael N. Starnbach

^* Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536; and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115

IFN- 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- during the first few days of infection. However, it was recently shown that a significant number of CD44^highCD8⁺ T cells also secrete IFN- 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- response and that cytosolic localization of Listeria was required to induce rapid IFN- production by CD44^highCD8⁺ 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- expression by CD8⁺ T cells. These results suggest that LLO expression is essential for induction of the early IFN- 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- 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- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health grants from the National Center for Research Resources (P20 RR20171; to S.E.F.D.), the National Institute of Allergy and Infectious Disease (AI055962; to M.N.S.), and by a pilot grant from the Harvard Digestive Diseases Center (DK34854; to S.E.F.D.).

² Address correspondence and reprint requests to Dr. Sarah E.F. D’Orazio, Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, 800 Rose Street–MS415, Lexington, KY 40536. E-mail address: sarah.dorazio{at}uky.edu

³ Abbreviations used in this paper: DC, dendritic cell; BMM, bone marrow-derived macrophage; CDC, cholesterol-dependent cytolysin; ICCS, intracellular cytokine staining; LB, Luria-Bertani; LLO, listeriolysin O; MOI, multiplicity of infection.

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