CD8 alpha- and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis.
In the early phase of leishmaniasis three types of potential antigen-presenting cells, including epidermal Langerhans cells (LC), dermal dendritic cells (DC) and inflammatory DC, are localized at the site of infection. Therefore, it has been a central question which cell type is responsible for the initiation of a protective immune response. In the early stage of an anti-Leishmania immune response, detectable Leishmania major antigen was localized in the paracortex of the draining lymph nodes (LN). Characterization of antigen-positive cells showed that L. major co-localized with DC of a CD11c(+) CD8 alpha(-) Langerin(-) phenotype. To determine the area of antigen uptake, dermis or epidermis, and to further define the type of antigen-transporting cells, L. major was inoculated subcutaneously and concurrently LC were mobilized with fluorescein isothiocyanate (FITC). After 3 days, DC carrying L. major antigen were always FITC(-), indicating a dermal and not an epidermal origin. Moreover, addition of L. major antigen to ex vivo isolated CD8 alpha(-) and CD8 alpha(+) DC from the draining LN of L. major-infected C57BL/6 mice demonstrated that both DC subpopulations were able to stimulate antigen-specific T cell proliferation in vitro. Without addition of exogenous antigen only the CD8 alpha(-) Langerin(-) DC were capable of stimulating antigen-specific T cell proliferation. Thus, we demonstrate that CD8 alpha(-) Langerin(-) DC and not LC are the basis of the protective immune response to intracellular L. major parasites in vivo.
Ritter
Uwe
U
Nachwuchsgruppe 1, Interdisziplinäres Zentrum für Klinische Forschung der Universität Erlangen-Nuremburg, Erlangen, Germany.
Meissner
Anja
A
Scheidig
Christina
C
Körner
Heinrich
H
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000096:biosynthesis / Q000276:immunology*; D016827:CD8 Antigens / Q000096:biosynthesis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000469:parasitology; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology*; D018320:Leishmania major / Q000235:genetics / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D037241:Mannose-Binding Lectins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D016053:RNA, Protozoan / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000469:parasitology
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D016827:CD8 Antigens; C431698:CD8alpha antigen; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D016053:RNA, Protozoan; D016650:Fluorescein-5-isothiocyanate