Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen‐specific T cells

Abstract

Murine epidermal Langerhans cells (LC) have been shown to internalizeLeishmania major, a cause of human cutaneous leishmaniasis, and to stimulate a vigorous parasite-specific T cell response. The present study emphasizes the critical role of LC in leishmaniasis by documenting directly that LC have the ability to transport L. major from the skin to the draining lymph node (LN). This was revealed by irreversible labeling of LC with a fluorescent cell linker and in vivo tracking. In contrast, no migration to the LN was seen with L. majorinfected macrophages. These findings were consistent with the results of mixed labeling immunohistology showing that early in infection the expression of parasite antigen in the LN draining the lesion was confined to dendritic cells and could not be detected in macrophages. Furthermore, dendritic cells in LN draining the site of cutaneous infection stimulated L. major-primed T cells in vitro and, most notably, were able to activate unprimed T cells capable of mediating parasite-specific delayed-type hypersensitivity reactivity in vivo . Taken together, the results indicate that LC capture L. major in the skin and transport it to the regional LN for initiation of the specific T cell immune response.

Dendritic Cell (DC)-Based Protection Against an Intracellular Pathogen Is Dependent Upon DC-Derived IL-12 and Can Be Induced by Molecularly Defined Antigens

“…DC have been shown to mediate the priming of Leishmania-specific T cells (49) and to produce high levels of IL-12 after exposure to parasite Ag (18,19), thus promoting the development of protective Th1 cells. To test the role of IL-12 production by the priming DC in the initiation of antileishmanial immunity after DC-mediated vaccination, we compared the protective efficacy of Ag-loaded LC from IL-12-deficient mice with that of LC obtained from WT mice.…”

Dendritic Cell-Derived IL-12p40 Homodimer Contributes to Susceptibility in Cutaneous Leishmaniasis in BALB/c Mice

“…Previous studies have shown that DC are capable of taking up L. major amastigotes and, to a lesser extent, promastigotes (10,(15)(16)(17). Infected DC were activated and released detectable amounts of IL-12p40 and IL-12p70 (10,11).…”

Dangerous liaisons: the role of “danger” signals in the immune response to gene therapy

“…6 They reside in an immature state in which they have high concentrations of Fc␥ and Fc⑀ receptors on their cell surface, and have been shown, in vitro, to be actively involved in phagocytosis and macropinocytosis, a process that enables sampling of the extracellular environment for solutes. [7][8][9][10] In this state they present only very low levels of major histocompatibility (MHC) molecules and other cell surface markers such as CD40, CD54 (intercellular adhesion molecule-1 [ICAM-1]), CD58 (lymphocyte function-associated antigen-3 [LFA-3]), CD80 (B7.1), and CD86 (B7.2). 11,12 Normally quiescent, they begin to migrate through a tissue in response to a barrage of cytokines that include tumor necrosis factor (TNF)-␣, interleukin (IL)-1␤, interferon (IFN)-␣, macrophage inflammatory protein (MIP)-1␣, and MIP-1␤.…”