The MASP Family of Trypanosoma cruzi: Changes in Gene Expression and Antigenic Profile during the Acute Phase of Experimental Infection

Abstract

Background Trypanosoma cruzi is the etiological agent of Chagas disease, a debilitating illness that affects millions of people in the Americas. A major finding of the T. cruzi genome project was the discovery of a novel multigene family composed of approximately 1,300 genes that encode mucin-associated surface proteins (MASPs). The high level of polymorphism of the MASP family associated with its localization at the surface of infective forms of the parasite suggests that MASP participates in host–parasite interactions. We speculate that the large repertoire of MASP sequences may contribute to the ability of T. cruzi to infect several host cell types and/or participate in host immune evasion mechanisms.MethodsBy sequencing seven cDNA libraries, we analyzed the MASP expression profile in trypomastigotes derived from distinct host cells and after sequential passages in acutely infected mice. Additionally, to investigate the MASP antigenic profile, we performed B-cell epitope prediction on MASP proteins and designed a MASP-specific peptide array with 110 putative epitopes, which was screened with sera from acutely infected mice.Findings and ConclusionsWe observed differential expression of a few MASP genes between trypomastigotes derived from epithelial and myoblast cell lines. The more pronounced MASP expression changes were observed between bloodstream and tissue-culture trypomastigotes and between bloodstream forms from sequential passages in acutely infected mice. Moreover, we demonstrated that different MASP members were expressed during the acute T. cruzi infection and constitute parasite antigens that are recognized by IgG and IgM antibodies. We also found that distinct MASP peptides could trigger different antibody responses and that the antibody level against a given peptide may vary after sequential passages in mice. We speculate that changes in the large repertoire of MASP antigenic peptides during an infection may contribute to the evasion of host immune responses during the acute phase of Chagas disease.

TcTASV-C, a Protein Family in Trypanosoma cruzi that Is Predominantly Trypomastigote-Stage Specific and Secreted to the Medium

“…On the other hand, the multigene family MASP was discovered when the parasite's genome was sequenced and annotated, and is a good example of how a genome project shed light into the structure of a genome [11], [17], [51]. Although the MASP family is composed by a very large number of genes (>1400), the delay in its identification was probably due to its unusual or not-so-abundant protein expression pattern.…”

The Trypanosoma cruzi Surface, a Nanoscale Patchwork Quilt

“…The trypomastigote coat is apparently formed by two juxtaposed layers of heavily O -glycosylated mucins and, underneath, glycoinositolphospholipids ( GIPLs) [9–11], with other less prevalent glycoproteins such as trans -sialidase (TS) [12], mucin-associated surface proteins (MASPs) [13], Gp85 surface glycoproteins [14], trypomastigote small surface antigen (TSSA) [15] and Tol-T antigens [16] speckled on this coat. All of these, except for the GIPLs, are encoded by highly polymorphic and developmentally-regulated gene families [17] bearing a similar predicted architecture, in which the outermost N- terminal adhesive domain likely protrudes from the ~15nm thick, mucin O -glycan canopy.…”

Neglected Tropical Diseases in the Post-Genomic Era

“…In this parasite, a large repository of antigenically distinct 'donor' VSGs, which are scattered along silent sites in the genome, are moved by recombination into an active VSG expression site [75]. By contrast, the intracellular parasite T. cruzi does not use this strategy of antigenic variation for host immune evasion but instead relies on the simultaneous display of multiple polymorphic glycoproteins (e.g., mucins, trans-sialidases, mucin-associated proteins) on its surface during its mammal-dwelling stages [22,76,77]. The presence of a mosaic antigenic coat could modulate the mammalian host immune response by impairing the development of highly-specific lymphocytes and/or facilitate the recognition of the broad spectrum of cell types and mammalian hosts infected by this parasite [22,76].…”

“…By contrast, the intracellular parasite T. cruzi does not use this strategy of antigenic variation for host immune evasion but instead relies on the simultaneous display of multiple polymorphic glycoproteins (e.g., mucins, trans-sialidases, mucin-associated proteins) on its surface during its mammal-dwelling stages [22,76,77]. The presence of a mosaic antigenic coat could modulate the mammalian host immune response by impairing the development of highly-specific lymphocytes and/or facilitate the recognition of the broad spectrum of cell types and mammalian hosts infected by this parasite [22,76]. Cumulative functional data (reviewed in [23]) and the recent finding of a significantly smaller number of gene copies encoding mucins, trans-sialidases, and mucin-associated proteins in the genome of a closely related species, the avirulent human-infective Trypanosoma rangeli further support a role for these molecules in T. cruzi pathogenesis [78].…”