title: T cell-derived IL-10 determines leishmaniasis disease outcome and is suppressed by a dendritic cell based vaccine.
abstract: In the murine model of Leishmania major infection, resistance or susceptibility to the parasite has been associated with the development of a Th1 or Th2 type of immune response. Recently, however, the immunosuppressive effects of IL-10 have been ascribed a crucial role in the development of the different clinical correlates of Leishmania infection in humans. Since T cells and professional APC are important cellular sources of IL-10, we compared leishmaniasis disease progression in T cell-specific, macrophage/neutrophil-specific and complete IL-10-deficient C57BL/6 as well as T cell-specific and complete IL-10-deficient BALB/c mice. As early as two weeks after infection of these mice with L. major, T cell-specific and complete IL-10-deficient animals showed significantly increased lesion development accompanied by a markedly elevated secretion of IFN-γ or IFN-γ and IL-4 in the lymph nodes draining the lesions of the C57BL/6 or BALB/c mutants, respectively. In contrast, macrophage/neutrophil-specific IL-10-deficient C57BL/6 mice did not show any altered phenotype. During the further course of disease, the T cell-specific as well as the complete IL-10-deficient BALB/c mice were able to control the infection. Furthermore, a dendritic cell-based vaccination against leishmaniasis efficiently suppresses the early secretion of IL-10, thus contributing to the control of parasite spread. Taken together, IL-10 secretion by T cells has an influence on immune activation early after infection and is sufficient to render BALB/c mice susceptible to an uncontrolled Leishmania major infection.
authors.affiliation: Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schwarz
authors.forename: Katharina A
authors.initials: KA
authors.lastname: Remer
authors.forename: Wiebke
authors.initials: W
authors.lastname: Nahrendorf
authors.forename: Anita
authors.initials: A
authors.lastname: Masic
authors.forename: Lisa
authors.initials: L
authors.lastname: Siewe
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.forename: Heidrun
authors.initials: H
authors.lastname: Moll
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D018320:Leishmania major / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000276:immunology* / Q000494:pharmacology; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C556062:IL10 protein, mouse; D054332:Leishmaniasis Vaccines; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma