Murine dendritic cells internalize Leishmania major promastigotes, produceIL-12 p40 and stimulate primary T cell proliferation in vitro

Metacyclic Leishmania promastigotes (PM), transmitted by sand-fly bite, are likely to interact initially with cells of the dendritic cell (DC) lineage (s) in the epidermis or dermis. Epidermal Langerhans cells internalize L. m ajor amastigotes (AM) and transport them to draining lymph nodes (Moll, H., Fuchs, H., Blank, C. and Rollinghoff, M., Eur: J. Immunol. 1993. 23: 1595) but little is known about the interaction of DC with PM. The present study demonstrates that DC are able to internalize PM and that the fate of the p arasites within DG differs from that within macrophages (M Phi). DC took up small numbers of PM which did not differentiate into AM but appeared to be degraded; M Phi internalized large numbers of PM into parasitophorous vacu oles where they differentiated into AM. In response to direct stimulation w ith PM, DC from both C3H ("resistant" to L. major infection) and BALB/c ("s usceptible") upregulated production of IL-12 p40. In contrast, IL-12 produc tion by M Phi was not detected. DC exposed to either metacyclic PM or PM cu lture supernatants were also able to stimulate proliferative responses in l ymph node T cells from naive mice. These data indicate that DC have the cap acity to promote protective Th1 immune responses in Leishmania infection an d suggest that DC exposed to PM may be useful in immunotherapy and vaccinat ion.