Mechanisms of evasion of Schistosoma mansoni schistosomula to the lethal activity of complement

Abstract

Schistosomula of Schistosoma mansoni became resistant to antibody-dependent complement damage in vitro after pre-incubation with normal human erythrocytes (NHuE) whatever the ABO or Rh blood group. Resistant parasites were shown to acquire host decay accelerating factor (DAF), a 70 kDa glycoprotein attached to the membrane of NHuE by a GPI anchor. IgG2a mAb anti-human DAF (IA10) immunoprecipitated a 70 kDa molecule from 125I-labeled schistosomula pre-incubated with NHuE and inhibited their resistance to complement-dependent killing in vitro. Incubation of schistosomula with erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNHE) or SRBC, which are DAF-deficient, did not protect the parasites from complement lesion. Supernatant of 100,000 x g collected from NHuE incubated for 24 h in defined medium was shown to contain a soluble form of DAF and to protect schistosomula from complement killing. Schistosomula treated with trypsin before incubation with NHuE ghosts did not become resistant to complement damage. On the other hand, pre-treatment with chymotrypsin did not interfere with the acquisition of resistance by the schistosomula. These results indicate that, in vitro, NHuE DAF can be transferred to schistosomula in a soluble form and that the binding of this molecule to the parasite surface is dependent upon trypsin-sensitive chymotrypsin-insensitive polypeptide(s) present on the surface of the worm.

Complement Resistance of Parasites

“…Also in vitro human DAF can be transferred to the scbistosomula of 5. mansoni [79]. Despite the glycolipid tail in DAF the transfer does not seem to occur passively, as trypsin, but not chymotrypsin pretreatment of schistosomula abolishes their ability to acquire DAF to the schistosomular surface [80] and schistosomula can have 1000fold more DAF/cell, than found, for example, on RBC [81]. Apparently, the transfer of DAF and possibly of the other glycolipid-tailed C inhibitor protectin provides a mechanism for S. mansoni to evade C attack in human blood.…”

Transcriptome of the parasitic flatworm Schistosoma mansoni during intra-mammalian development

“…To date, a S. mansoni gene with sequence or structural similarity to CFI has not been described, but the parasites do possess a serine protease, m28, that cleaves C3bi (a function normally carried out by CFI [68,89]). For DAF, a native S. mansoni form has not been reported but schistosomes can acquire DAF from host blood cells [90,91]. Given the nature of other genes sharing its expression pattern, the structural match to human CFH, and its phylogenetic relationship, it is tempting to speculate that the CFH-like gene in schistosomes may have a role in immunomodulation.…”

Complement Evasion: An Effective Strategy That Parasites Utilize to Survive in the Host

“…When incubated with normal human erythrocytes, but not with DAF-deficient erythrocytes, S. mansoni became resistant to complement lysis in vitro (Horta and Ramalho-Pinto, 1991). Further study showed that S. mansoni acquired DAF from host erythrocytes via the expression of a GPI anchor on the surface of the worm (Ramalho-Pinto et al, 1992). The ability of the trypsin-treated S. mansoni worm to acquire DAF was reduced (Ramalho-Pinto et al, 1992).…”

“…Further study showed that S. mansoni acquired DAF from host erythrocytes via the expression of a GPI anchor on the surface of the worm (Ramalho-Pinto et al, 1992). The ability of the trypsin-treated S. mansoni worm to acquire DAF was reduced (Ramalho-Pinto et al, 1992). Treatment with GPI-specific phospholipase D (GPI-PLD) facilitated the binding of DAF to the surface of the schistosomula (Carvalho et al, 1994).…”