title: IL-17 promotes progression of cutaneous leishmaniasis in susceptible mice.
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-beta1 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-gamma 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.
authors.affiliation: Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Susanna
authors.initials: S
authors.lastname: Lopez Kostka
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dinges
authors.forename: Klaus
authors.initials: K
authors.lastname: Griewank
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Mark C
authors.initials: MC
authors.lastname: Udey
authors.forename: Esther
authors.initials: E
authors.lastname: von Stebut
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D007111:Immunity, Cellular / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053759:Interleukin-23 / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D013045:Species Specificity; D018418:Th2 Cells / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23