Apoptosis in parasites and parasite-induced apoptosis in the host immune system: a new approach to parasitic diseases

Apoptosis, a form of programmed cell death (PCD), has been described as essential for normal organogenesis and tissue development, as well as for the proper function of cell-renewal systems in adult organisms. Apoptosis is also pivotal in the pathogenesis of several different diseases. In this paper we discuss, from two different points of view, the role of apoptosis in parasitic diseases. The description of apoptotic death in three different species of heteroxenic trypanosomatids is reviewed, and considerations on the phylogenesis of apoptosis and on the eventual role of PCD on their mechanism of pathogenesis are made. From a different perspective, an increasing body of evidence is making clear that regulation of host cell apoptosis is an important factor on the definition of a host-pathogen interaction. As an example, the molecular mechanisms by which Trypanosoma cruzi is able to induce apoptosis in immunocompetent cells, in a murine model of Chagas' disease, and the consequences of this phenomenon on the outcome of the experimental disease are discussed.

Immune evasion by Trypanosomatidae: normal aggregated immunoglobulin protects against lysis by the alternative complement pathway

Immunoglobulin Fc receptors (FcRs), present in Trypanosomatidae pathogenic for mammals, may be a mechanism by which these parasites escape the host immune response. We studied the possible role of these receptors in evasion by the alternative complement pathway. Promastigotes of Leishmania amazonensis and trypsinized trypomastigotes of Trypanossoma cruzi treated with heat-aggregated normal gamma globulin and then incubated with fresh normal guinea pig serum were shown to be more resistant to lysis. When compared to log phase Leishmania promastigotes, this resistance was at least 4.5-fold greater in parasites harvested in the stationary growth phase EDTA and egta PLUS MgCl2 inhibited the cytotoxic effect of serum, suggesting the participation of the alternative complement pathway. The distribution of FcRs among genera of Trypanosomatidae that arepathogenic, infective or noninfective for mammals and their affinity for mammalian and fowl immunoglobulin were also examined. These receptors ara presented only in species infective or pathogenic for mammals, a finding that suggests that this structure is essential for the establishment of infection but in not necessarily a virulence factor. Further more, the ligand specificity is limited to the immunoglobulin of mammalian but not of fowl origin