Impaired macrophage listericidal and cytokine activities are responsible for the rapid death of Listeria monocytogenes-infected IFN-gamma receptor-deficient mice

J Immunol. 1997 Jun 1;158(11):5297-304.


IFN-gamma receptor-deficient (IFN-gammaR -/-) mice were used to study the innate immune responses during infection with Listeria monocytogenes. Mutant mice were unable to limit bacterial growth and died of sepsis even with an infection dose of 70 Listeria. At day 2, they showed an exacerbated listeriosis and mice succumbed to infection before the onset of an effective specific immunity, demonstrating a defective innate immunity. Recruitment and extravasation of phagocytic cells to infected organs was present and dominated by neutrophils. However, during the early course of infection, mutant mice responded by an elevated inflammatory type 1 cytokine response, as determined by IL-12, IFN-gamma, TNF-alpha, and IL-1alpha-specific RNA expression. Induction of inducible nitric oxide synthase was present and also increased in mutant mice. Interestingly, IFN-gammaR -/- neutrophils expressed substantial TNF-alpha- and IL-1alpha-specific RNA, suggesting a substantial contribution in the overall inflammatory cytokine response. In contrast, IFN-gammaR -/- macrophages showed reduced MHC class II surface expression levels and impaired TNF-alpha and IL-1alpha but normal IL-6 production after restimulation with heat-killed L. monocytogenes. Moreover, IFN-gammaR -/- macrophages showed defective listericidal activities. In contrast to normal macrophages, Listeria escaped rapidly from the phagosome in IFN-gammaR -/- macrophages to the cytoplasm, where they productively survived. In conclusion, these data suggest that IFN-gammaR signaling activates yet unknown functions in macrophages, preventing Listeria-induced escape from the phagosome and consequent killing of the invader. Together with the impaired cytokine responses, these macrophage defects seem to be responsible for the dramatic susceptibility during innate immunity, whereas predominant neutrophil responses mediate limited protective role in mutant mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / immunology*
  • Immunity, Cellular
  • Listeria monocytogenes*
  • Listeriosis / immunology*
  • Listeriosis / pathology
  • Macrophages / immunology*
  • Macrophages / microbiology
  • Mice
  • Mice, Mutant Strains
  • Phagocytosis / immunology
  • Receptors, Interferon / deficiency
  • Receptors, Interferon / immunology*


  • Cytokines
  • Receptors, Interferon
  • interferon gamma receptor