A role for leukocyte-derived IL-1RA in DC homeostasis revealed by increased susceptibility of IL-1RA-deficient mice to cutaneous leishmaniasis

J Invest Dermatol. 2011 Aug;131(8):1650-9. doi: 10.1038/jid.2011.99. Epub 2011 Apr 28.


Dendritic cell (DC)-derived IL-1α/β plays a critical role in the induction of T helper type 1 (Th1)-dependent immunity against Leishmania. DCs from susceptible BALB/c mice produce less IL-1α/β when compared with resistant C57BL/6 mice, contributing to aberrant Th2 development and ultimate death of infected mice. We have extended our studies of the role of IL-1 in leishmaniasis using IL-1RA(-/-) BALB/c mice that are characterized by upregulated IL-1 receptor signaling. Unexpectedly, infection of IL-1RA(-/-) mice led to significantly worsened disease outcome with larger lesions, dramatically higher parasite burdens, and decreased IFN-γ production by antigen-specific T cells. We determined that IL-1RA(-/-) DCs were more mature already in the steady state, exhibited less phagocytotic capacity, and IL-12 production in response to various stimuli was impaired. Our data suggest that in addition to effects on Th education, IL-1α/β signaling also modulates DC homeostasis with increased signaling, leading to downmodulation of IL-12 synthesis and worsened disease outcome after infection with Leishmania major. Thus, the complex regulation of various members of the IL-1 cytokine family mediated through effects on both DCs and T cells critically contributes to disease outcome against this important human pathogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / parasitology
  • Dendritic Cells / immunology*
  • Dendritic Cells / parasitology
  • Disease Susceptibility / immunology
  • Immunophenotyping
  • Interleukin 1 Receptor Antagonist Protein / genetics*
  • Interleukin 1 Receptor Antagonist Protein / immunology*
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Phagocytosis / immunology
  • Th1 Cells / immunology*
  • Th1 Cells / parasitology


  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-12