Complement-mediated lysis of Trypanosoma cruzi trypomastigotes by human anti-alpha-galactosyl antibodies.

Abstract

Antibodies that lyse trypomastigotes in a complement-mediated reaction are believed to be the main participants in the protection against virulent Trypanosoma cruzi. Antibodies with a specificity for alpha-galactosyl-containing determinants--generally called antiGal--were studied to determine their role in the lysis of trypomastigote forms. The titers of antiGal markedly increase in Chagas's disease. In the present study we demonstrate binding of this antibody to T. cruzi and the complement-mediated lysis of trypomastigotes by antiGal. Lysis of metacyclic trypomastigotes by whole Chagasic (Ch) serum or isolated antiGal fractions was equally inhibited by alpha- but not by beta-galactosides. Most of the lytic power of the Ch antiGal as well as of the whole Ch serum was removed by absorption on Synsorb-linked Gal alpha 1, 3Gal beta 1, 4GlcNAc followed by rabbit erythrocyte absorption. The Ch antiGal had a lower affinity for melibiose bound to agarose than for the trisaccharide linked to Synsorb, and was several times more effective in the immunolysis of trypomastigotes than the corresponding antiGal from normal human serum. Lytic antibodies were partly absorbed by Serratia marcescens but not by Escherichia coli O111. A human volunteer immunized with an S. marcescens vaccine elicited a specific antiGal response that was lytic to trypomastigotes (70% lysis). We suggest that in vivo high-affinity antiGal antibody clones, as occur in Ch patients, may significantly contribute to the destruction of the parasite, whereas low-affinity antiGal clones are much less effective in the protection against T. cruzi infection.

Antibody production and tolerance to the α-gal epitope as models for understanding and preventing the immune response to incompatible ABO carbohydrate antigens and for α-gal therapies

“…No toxic or other detrimental effects were caused by the prolonged high anti-Gal activity in the implanted patients. Activation of anti-Gal B cells for production of elicited anti-Gal was also observed in humans infected with protozoa presenting α-gal-like epitopes, such as Trypanosoma ( Towbin et al, 1987 ; Milani and Travassos, 1988 ; Avila et al, 1989 ; Almeida et al, 1991 ; Almeida et al, 1994 ) and Leishmania ( Avila et al, 1989 ). Elevated anti-Gal activity was shown to induce effective complement-mediated cytolysis of Trypanosoma ( Milani and Travassos, 1988 ; Almeida et al, 1991 ; Almeida et al, 1994 ).…”

Guidelines for the purification and characterization of extracellular vesicles of parasites

“…The column is eluted with 100 mM ammonium acetate pH 6.5 and up to 80 fractions (1 mL each) are collected. The T. cruzi EVs can be detected for their reactivity in chemiluminescent (CL‐ELISA) with specific antibodies such as the anti‐α‐Gal Abs found in the sera of CD patients, which recognize terminal nonreducing α‐galactosyl residues on the highly abundant tGPI‐mucins (Almeida et al., 1994 , 1991 ). Trypomastigote EVs are highly reactive with these antibodies (Nogueira et al., 2015 ; Trocoli Torrecilhas et al., 2009 ).…”

Importance of Probiotics in Fish Aquaculture: Towards the Identification and Design of Novel Probiotics

“…The oligosaccharide α-Gal has recently gained significant attention in the scientific community [ 100 ] due to its role as a major antigen responsible for protective immunity against α-Gal-expressing pathogens that affect humans (e.g., Trypanosoma spp. [ 101 ], Leishmania spp. [ 102 ], and Plasmodium spp.…”