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

Sarah E.F. D'Orazio, Matthew J. Troese, Michael N. Starnbach

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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 CD44highCB8+ 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.

Original languageEnglish
Pages (from-to)7146-7154
Number of pages9
JournalJournal of Immunology
Volume177
Issue number10
DOIs
StatePublished - Nov 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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