Interleukin 1α promotes TH1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice

Esther Von Stebut, Jan M. Ehrchen, Yasmine Belkaid, Susanna Lopez Kostka, Katharina Mölle, Jürgen Knop, Cord Sunderkötter, Mark C. Udey

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Protective immunity against pathogens such as Leishmania major is mediated by interleukin (IL)-12-dependent Th1-immunity. We have shown previously that skin-dendritic cells (DCs) from both resistant C57BL/6 and susceptible BALB/c mice release IL-12 when infected with L. major, and infected BALB/c DCs effectively vaccinate against leishmaniasis. To determine if cytokines other than IL-12 might influence disease outcome, we surveyed DCs from both strains for production of a variety of cytokines. Skin-DCs produced significantly less IL-1α in response to lipopolysaccharide/interferon γ or L. major when expanded from BALB/c as compared with C57BL/6 mice. In addition, IL-1α MRNA accumulation in lymph nodes of L. major-infected BALB/c mice was ∼3-fold lower than that in C57BL/6 mice. Local injections of IL-1α during the first 3 d after infection led to dramatic, persistent reductions in lesion sizes. In L. major-infected BALB/c mice, IL-1α administration resulted in increased Th1- and strikingly decreased Th2-cytokine production. IL-1α and IL-12 treatments were similarly effective, and IL-1α efficacy was strictly IL-12 dependent. These data indicate that transient local administration of IL-1α acts in conjunction with IL-12 to influence Th-development in cutaneous leishmaniasis and prevents disease progression in susceptible BALB/c mice, perhaps by enhancing DC-induced Th1-education. Differential production of IL-1 by C57BL/6 and BALB/c mice may provide a partial explanation for the disparate outcomes of infection in these mouse strains.

Original languageEnglish
Pages (from-to)191-199
Number of pages9
JournalJournal of Experimental Medicine
Volume198
Issue number2
DOIs
StatePublished - Jul 21 2003

Keywords

  • Dendritic cell
  • IL-1
  • Infection
  • Leishmania major
  • T helper cell type 1/T helper cell type 2 immune response

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