Development and regulation of cell-mediated immunity in experimental leishmaniasis.
The development of a Th1 response is critical for controlling many intracellular pathogens. Our laboratory has focused on the role IL-12 plays in initiating such a Th1 response following infection with the obligate intracellular protozoan, Leishmania. Infection of several mouse strains with L. major is associated with IL-12 production and the development of a Th1 response and resistance, although, interestingly, some species of Leishmania (L. mexicana and L. amazonenesis) fail to initiate a Th1 response in the same mouse strains. Consistent with these observations was our finding that IL-12 is an effective adjuvant for the induction of a Th1 response in leishmaniasis (1). Surprisingly, however, in spite of the fact that following resolution of a primary leishmanial infection there is substantial and long-lived resistance to reinfection, an effective prophylactic or therapeutic vaccine for human leishmaniasis does not exist. Our ability to induce a Th1 response in a primate Leishmania vaccine model, but not protection, suggests that long-term resistance to Leishmania requires more than simply initiating a Th1 response (2). Therefore, we recently expanded our studies to investigate how infection-induced resistance to Leishmania operates. We made the unexpected finding that IL-12 is required for L. major-infected mice to remain immune (3). We are now studying how IL-12 participates in maintaining cell-mediated immunity, and more broadly, how immunologic memory works in L. major-healed mice, as well as defining parasite factors that may block the development of cell-mediated immunity.
Scott
Phillip
P
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. pscott@vet.upenn.edu
D000818:Animals; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate / Q000276:immunology; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000276:immunology; D007896:Leishmaniasis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000821:virology
D018664:Interleukin-12