Impaired Th1 responses in mice deficient in Epstein-Barr virus-induced gene 3 and challenged with physiological doses of Leishmania major

Sabine Zahn, Stefan Wirtz, Mark Birkenbach, Richard S. Blumberg, Markus F. Neurath, Esther von Stebut

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Protection against Leishmania major is dependent on IL-12 release from L. major-infected dendritic cells (DC) that induce IFN-γ-producing Th1/Tc1 cells. IL-27, a novel member of the IL-12 family, is a heterodimer composed of p28 and IL-12p40-related Epstein-Barr virus-induced gene 3 (EBI3), and was shown to be produced by DC. In this study, we utilized EBI3-deficient mice to investigate the role of IL-27 in leishmaniasis using physiological low-dose infections that mimic natural transmissions. Lesions in EBI3-/- mice were significantly larger between weeks 3 and 10 post infection, reaching up to approximately threefold increased lesion volumes compared to wild types. In parallel, dermal lesions of EBI3-/- mice contained greater parasite numbers, reaching a peak load that was 2-log higher than in C57BL/6 mice. However, lesions in EBI3-/- and wild-type mice resolved after 12 weeks. At early time points, the antigen-specific cytokine response in EBI3-/- lymph nodes showed increased levels of IL-4, IL-10 and IL-13 and decreased IFN-γ production. IL-27 production was restricted to the DC population, since the majority of EBI3 expression in lymph nodes of infected mice was found in CD11c+ cells. In conclusion, our data show that DC-derived IL-27 is critical for the timely initiation of efficient anti-parasite Thq immunity early in infections.

Original languageEnglish (US)
Pages (from-to)1106-1112
Number of pages7
JournalEuropean Journal of Immunology
Volume35
Issue number4
DOIs
StatePublished - Apr 2005

Keywords

  • Dendritic cell
  • IL-12
  • IL-27
  • Leishmania major
  • Th1/Th2

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