IL-17 mediates immunopathology in the absence of IL-10 following Leishmania major infection

PLoS Pathog. 2013 Mar;9(3):e1003243. doi: 10.1371/journal.ppat.1003243. Epub 2013 Mar 21.


Leishmaniasis, resulting from infection with the protozoan parasite Leishmania, consists of a wide spectrum of clinical manifestations, from healing cutaneous lesions to fatal visceral infections. A particularly severe form of cutaneous leishmaniasis, termed mucosal leishmaniasis, exhibits decreased IL-10 levels and an exaggerated inflammatory response that perpetuates the disease. Using a mouse model of leishmaniasis, we investigated what cytokines contribute to increased pathology when IL-10-mediated regulation is absent. Leishmania major infected C57BL/6 mice lacking IL-10 regulation developed larger lesions than controls, but fewer parasites. Both IFN-γ and IL-17 levels were substantially elevated in mice lacking the capacity to respond to IL-10. IFN-γ promoted an increased infiltration of monocytes, while IL-17 contributed to an increase in neutrophils. Surprisingly, however, we found that IFN-γ did not contribute to increased pathology, but instead regulated the IL-17 response. Thus, blocking IFN-γ led to a significant increase in IL-17, neutrophils and disease. Similarly, the production of IL-17 by cells from leishmaniasis patients was also regulated by IL-10 and IFN-γ. Additional studies found that the IL-1 receptor was required for both the IL-17 response and increased pathology. Therefore, we propose that regulating IL-17, possibly by downregulating IL-1β, may be a useful approach for controlling immunopathology in leishmaniasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-17 / blood
  • Interleukin-17 / immunology*
  • Interleukin-1beta / metabolism
  • Leishmania major / pathogenicity
  • Leishmania major / physiology*
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / metabolism
  • Leishmaniasis, Cutaneous / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / immunology
  • Neutrophil Infiltration


  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-10
  • Interferon-gamma