Mechanisms for the elimination of potentially lytic complement-fixing variable surface glycoprotein antibody-complexes inTrypanosoma brucei

Abstract

Live antibody-coated Trypanosoma brucei parasites remove variable surface glycoprotein (VSG)-antibody complexes from their surface upon warming to 37 degrees C and evade antibody-activated complement lysis by both protein synthesis-dependent and protein synthesis-independent mechanisms. The protein synthesis-dependent process follows antibody-mediated trypanosome agglutination, whereas the protein synthesis-independent mechanism can occur in the absence of trypanosome agglutination. The latter process leads to a more rapid elimination of complement-fixing VSG-antibody complexes.

Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein inTrypanosoma brucei

“…Endocytosis may be important for removing anti-VSG antibodies from the cell surface (Russo et al, 1993;O'Beirne et al, 1998); that is, up to a certain antibody level in the blood, the parasites may be able to evade Fc-receptor-mediated phagocytosis by macrophages. In fact, quantification in vitro of the rate of antibody endocytosis/degradation shows remarkably rapid kinetics of anti-VSG-IgG endocytosis (M.E., unpublished).…”

“…VSG is conveyed to endosomes by coated vesicles and indirect evidence suggests that it is efficiently recycled (Webster and Grab, 1988;Frevert and Reinwald, 1988;Seyfang et al, 1990;Grünfelder et al, 2003). Moreover, T. brucei clears anti-VSG antibodies from the cell surface (Russo et al, 1993;O'Beirne et al, 1998), and this process, in addition to the well-known antigenic variation, may contribute to parasite persistence in the immuno-competent host.…”

Expression and Function of the Trypanosoma brucei Major Surface Protease (GP63) Genes

“…Another consideration is that bloodstream trypanosomes are resistant to complement-mediated lysis via the alternate pathway, and one of the roles of MSPs in Leishmania is to bind complement component C3 and proteolytically convert C3b to an inactive form, thus interrupting the complement cascade (13). The dense VSG coat of bloodstream trypanosomes is one factor contributing to their complement resistance (55,56), but one or more of the three TbMSPs also might be involved. As inhibiting TbMSP-B expression in bloodstream cells had no observable effect and TbMSP-B is the only MSP expressed in complement-sensitive procyclic cells, it seems unlikely that TbMSP-B can account for either of these observations.…”

Proteases from Trypanosoma brucei brucei

“…Nagana is still of great economic importance in Africa, where it prevents livestock farming in many areas, and certain parts of Africa are experiencing a large resurgence in human trypanosomiasis (Walgate, 1994). While the parasite's major lysosomal cysteine proteinase (trypanopain) is considered a potentially important factor in the development of the disease (AuthiC et al, 1993;Russo et al, 1994), the role of a cytoplasmic serine oligopeptidase (which we call oligopeptidase-Tb, OP-Tb) has not yet been explored.…”

“…Additionally, the enzyme is proposed to help the parasite escape opsonisation by degrading internalised antibody-variant surface glycoprotein complexes (Russo et al, 1994). Enzyme released into the host bloodstream…”