FIGURE 1.

The process of granuloma maturation during L. donovani infection. The infection of resident liver macrophages (Kupffer cells; KCs) initiates the process of granulomatous inflammation (initiation). Hepatic NKTs migrate toward infected KCs and their interaction triggers the recruitment of mononuclear cells to the liver (amplification). Various cell types, predominantly T cells, are recruited to infected KC foci within the liver, with granulomas developing in size and cellularity in an asynchronous manner over the first 4 weeks post-infection (p.i.) (maturation). During the maturation stage, the inflammatory response peaks around 4 weeks p.i. where the antileishmanial response becomes sufficient to begin clearing the parasite burden. As parasites are cleared from individual infected KC foci, cells begin to move out of the granuloma, returning the liver to its original pre-infection state. Hepatic granulomatous inflammation resolves by 8 weeks p.i. with the majority of parasites cleared. Data on parasite load and granuloma maturation redrawn from Murray (2001). KC, Kupffer cell; IM, immature granuloma; M, mature granuloma; sterile, sterile granuloma.