Fig. 5.

Intracellular amastigotes are unexpectedly resistant to NO killing. PEMs were either pretreated with IFN-γ and LPS 2 h before infection with metacyclic promastigote-stage parasites (promastigotes, open bars) or were first infected with metacyclic-stage parasites and then treated with IFN-γ and LPS 72 h after infection (amastigotes, gray bars). NO production (A) and the number of parasites per infected MФ were determined by microscopy 24 h after IFN γ/LPS treatment. (B) The percent of parasites remaining relative to that seen in untreated MФs at the same time point. Graphs show mean ± SEM; *P < 0.05; n.s., not significant by Student’s t test. (C) Model of Leishmania persistence and concomitant immunity. Persistent Leishmania (green oval) are found in two populations. The first population replicates similarly to parasites in acute infections, whereas the other population replicates very slowly and may be quiescent. Although some of the progeny of the replicating parasites repopulate the replicating or quiescent parasite pools, many progeny parasites are killed. Parasite replication serves to maintain persistence while simultaneously providing a continuous supply of Leishmania antigen, resulting in life-long immune stimulation.