Leishmania major-infected murine Langerhans cell-like dendritic cells fromsusceptible mice release IL-12 after infection and vaccinate against experimental cutaneous Leishmaniasis

Leishmania major-infected C57BL/6 skin-dendritic cells (DC) are activated a nd release cytokines (including IL-12 p70), and likely initiate protective Th1 immunity in vivo (von Stebut, E. et al., J. Exp. Med. 188: 1547-1552). To characterize differences in DC function in mice that are genetically sus ceptible (BALB/c) and resistant (C57BL/6) to cutaneous leishmaniasis, eve a nalyzed the effects of L. major on Langerhans cell-like, fetal skin-derived DC (FSDDC) from both strains. BALB/c- and C57BL/6-FSDDC ingested similar n umbers of amastigotes, but did not ingest metacyclic promastigotes. Like C5 7BL/6-FSDDC, infection of BALB/c-FSDDC led to up-regulation of MHC class I and II antigens, CD40, CD54, and CD86 within 18 h. L. major-induced BALB/c DC activation also led to the release of TNF-alpha, IL-6 and IL-12 p40 into 18-h supernatants. Infected BALB/c- and C57BL/6-DC both released small amo unts of IL-12 p70 within 72 h. Additional stimulation with IFN-gamma and/or anti-CD40 induced the release of more IL-12 p70 from infected BALB/c-DC th an C57BL/6-DC. Coculture of control or infected BALB/c- and C57BL/6-DC with naive syngeneic CD4(+) T cells and soluble anti-CD3 resulted in mixed, IFN -gamma -predominant responses after restimulation with immobilized anti-CDS . Finally syngeneic L. major-infected DC effectively vaccinated BALB/c mice against cutaneous leishmaniasis. Genetic susceptibility to L. major that r esults from induction of Th2 predominant immune responses after infection d oes not appear to reflect failure of skin DC to internalize or respond to p arasites, or the inability of BALB/c T cells to mount a Th1 response to DC- associated Leishmania antigens.