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* Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany;
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Japan; and
Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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-
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grants SFB 490 and SFB 548 from the Deutsche Forschungsgemeinschaft and the Berliner Stiftung für Dermatologie (to E.v.S.). M.C.U. is supported by the Intramural Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health.
2 S.L.K. and S.D. have contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Esther von Stebut, Department of Dermatology, Johannes Gutenberg-University, Langenbeckstrasse 1, 55131 Mainz, Germany. E-mail address: vonstebu{at}mail.uni-mainz.de
4 Abbreviations used in this paper: M
, macrophage; LN, lymph node; SLA, soluble Leishmania Ag; DC, dendritic cell; EAE, experimental autoimmune encephalitis; IL-17A, IL-17 antagonist.
This article has been cited by other articles:
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  C. F. Anderson, J. S. Stumhofer, C. A. Hunter, and D. Sacks IL-27 Regulates IL-10 and IL-17 from CD4+ Cells in Nonhealing Leishmania major Infection J. Immunol., October 1, 2009; 183(7): 4619 - 4627. [Abstract] [Full Text] [PDF]
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