title: Hierarchy of susceptibility of dendritic cell subsets to infection by Leishmania major: inverse relationship to interleukin-12 production.
abstract: Dendritic cells (DCs) are professional antigen-presenting cells which initiate and regulate T-cell immune responses. Here we show that murine splenic DCs can be ranked on the basis of their ability to phagocytose and harbor the obligately intracellular parasite Leishmania major. CD4(+) CD8(-) DCs are the most permissive host cells for L. major amastigotes, followed by CD4(-) CD8(-) DCs; CD4(-) CD8(+) cells are the least permissive. However, the least susceptible CD4(-) CD8(+) DC subset was the best interleukin-12 producer in response to infection. Infection did not induce in any DC subset production of the proinflammatory cytokine gamma interferon and nitric oxide associated with the induction of Th1 responses. The number of parasites phagocytosed by DCs was low, no more than 3 organisms per cell, compared to more than 10 organisms per macrophage. In infected DCs, the parasites are located in a parasitophorous vacuole containing both major histocompatibility complex (MHC) class II and lysosome-associated membrane protein 1 molecules, similar to their location in the infected macrophage. The parasite-driven redistribution of MHC class II to this compartment indicates that infected DCs should be able to present parasite antigen.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Henri
authors.forename: Joan
authors.initials: J
authors.lastname: Curtis
authors.forename: Hubertus
authors.initials: H
authors.lastname: Hochrein
authors.forename: David
authors.initials: D
authors.lastname: Vremec
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.forename: Emanuela
authors.initials: E
authors.lastname: Handman
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D018664:Interleukin-12 / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000469:parasitology; D018320:Leishmania major / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D018664:Interleukin-12; D009569:Nitric Oxide