Transformation ofLeishmania mexicanametacyclic promastigotes to amastigote-like forms mediated by binding of human C-reactive protein

Abstract

Infective metacyclic promastigote forms ofLeishmania mexicanaare introduced by the bite of sandfly vectors into their human hosts where they transform into the amastigote form. The kinetics of this process was examinedin vitroin response to different combinations of temperature (26 °C or 32 °C), pH (7.2 or 5.5), and exposure to human serum. Little transformation occurred at 26 °C/pH 7.2, intermediate levels at 26 °C/pH 5.5 and 32 °C/ pH 7.2, and the greatest response at 32 °C/pH 5.5. Transformation was stimulated by exposure to normal human serum, but was markedly reduced when serum previously incubated at 56 °C for 1 h was used (complement heat-inactivated). This stimulatory effect was reproduced by exposure to a single purified component of human serum, C-reactive protein (CRP). Binding of CRP to the whole surface ofL. mexicanametacyclic promastigotes, including the flagella, was demonstrated by an indirect fluorescent antibody test. The effect of purified CRP was dose dependent and occurred using normal serum concentrations. The stimulatory effect of whole serum was oblated by CRP depletion and restored by addition of purified CRP. The effects of cAMP analogues indicated that transformation could be mediated via an adenylate cyclase cascade.