Increased infectivity of stationary-phase promastigotes of Leishmania donovani: correlation with enhanced C3 binding capacity and CR3-mediated attachment to host macrophages.

This study demonstrated that the greater infectivity of stationary-phase promastigotes of Leishmania donovani is related to increased complement fixation on the parasite surface, resulting in increased binding to host mononuclear phagocytes (MPs) via complement type 3 receptors (CR3). The in vivo infectivity of log- and stationary-phase promastigotes was compared by measuring parasite loads in the livers of BALB/c mice 14 days after i.v. inoculation. The same populations were tested for their ability to bind to resident murine peritoneal macrophages (RPM) in vitro during a 20-min serum-free incubation period. Stationary-phase parasites displayed both higher in vivo infectivity and increased in vitro binding. However, following uptake by RPM, no significant difference in the 72 hr survival of the two populations could be detected. The in vitro binding of log and stationary parasites was uniformly inhibited in the presence of a mAb (M1/70) specific for CR3, confirming that the interaction of this receptor with its ligand, iC3b, plays a vital role in initial attachment of both promastigote populations. Following incubation with a human serum source, the amount of ligand appeared to be greater on the surface of stationary-phase promastigotes, as indicated by their ability to trigger the alternative complement pathway and by solid-phase ELISA measurements using antiserum specific for human C3. Collectively, these findings suggest that the infectivity of L. donovani promastigotes is influenced by the extent of initial attachment to host MPs, as determined by the levels of complement deposition and subsequent CR3-mediated binding.