IL-17 promotes progression of cutaneous leishmaniasis in susceptible mice

Susanna Lopez Kostka, Stephanie Dinges, Klaus Griewank, Yoichiro Iwakura, Mark C. Udey, Esther Von Stebut

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

Resistance to leishmaniasis in C57BL/6 mice depends on Th1/Tc1 cells. BALB/c mice preferentially develop Th2 immunity and succumb to infection. We now assessed the role of IL-17 in cutaneous leishmaniasis. During the course of Leishmania major infection, BALB/c CD4 cells and neutrophils produced increased amounts of IL-17 as compared with cells from C57BL/6 mice. This increase was associated with significantly increased IL-23 release from L. major-infected BALB/c dendritic cells (DC), whereas IL-6 and TGF-β1 production by BALB/c and C57BL/6 DC were comparable. Interestingly, lesion sizes in infected IL-17-deficient BALB/c mice were dramatically smaller and failed to progress as compared with those in control mice. Similar amounts of IL-4, IL-10, and IFN-γ were produced by T cells from IL-17-deficient mice and control mice consistent with development of Th2-predominant immunity in all animals. Improved disease outcome was associated with decreased CXCL2-accumulation in lesion sites and decreased neutrophil immigration into lesions of infected IL-17-deficient mice confirming prior observations that enhanced neutrophil recruitment contributes to disease susceptibility in BALB/c mice. This study excludes an important facilitating role for IL-17 in Th1/Th2 development in L. major-infected BALB/c mice, and suggests that IL-23 production by L. major-infected DC maintains IL-17+ cells that influence disease progression via regulation of neutrophil recruitment.

Original languageEnglish
Pages (from-to)3039-3046
Number of pages8
JournalJournal of Immunology
Volume182
Issue number5
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

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    Kostka, S. L., Dinges, S., Griewank, K., Iwakura, Y., Udey, M. C., & Von Stebut, E. (2009). IL-17 promotes progression of cutaneous leishmaniasis in susceptible mice. Journal of Immunology, 182(5), 3039-3046. https://doi.org/10.4049/jimmunol.0713598