Pathogen diversity, immunity, and the fate of infections: lessons learned from Trypanosoma cruzi human–host interactions

Magalhães, Luísa Mourão Dias; Gollob, Kenneth J.; Zingales, Bianca; Dutra, Walderez Ornelas

doi:10.1016/s2666-5247(21)00265-2

Cited by 39 publications

(49 citation statements)

References 100 publications

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“…With NGP11b in hand, its suitability as a diagnostic BMK was assessed and compared with purified tGPI-MUC from the mammal-dwelling trypomastigote stage of T. cruzi Colombiana (TcI tGPI-MUC) and Y (TcII tGPI-MUC) strains, as described in Materials and Methods. We used tGPI-MUC preparations from these two genotypes because they are responsible for most T. cruzi infections in North, Central, and South America and Spain [ 14 ]. Moreover, since most of the CCD serum samples used in this study were from Venezuela and Mexico, we evaluated whether there was any difference in the immunoreactivity to NGP11b (29 GU/BSA) in comparison with that to TcI tGPI-MUC and TcII tGPI-MUC.…”

Section: Resultsmentioning

confidence: 99%

“…Likewise, CCD sera of Venezuela (light pink circles, n = 42), which were diagnosed only by CS, showed a comparable trend, that is, ~93% (39/42), ~88% (37/42), and ~52% (22/42) were positive for NGP11b, TcI tGPI-MUC, and TcII tGPI-MUC, respectively ( Figure 2 B). Since most patients of the Mexico and Venezuela panel were likely infected with TcI, which is a highly prevalent genotype infecting people in these countries [ 14 ], these results indicate that NGP11b could be a very promising diagnostic BMK to be used in countries where the highly diverse TcI genotype is predominant.…”

Section: Resultsmentioning

confidence: 99%

“…Considerable variation in the immunological and biological properties and expression of the terminal, nonreducing α-Gal glycotopes have previously been observed in tGPI-MUC purified from Colombiana (TcI) and Y (TcII) strains [ 14 , 48 ]. In this study, we observed a similar immunoreactivity (no significant difference) to NGP11b and TcI tGPI-MUC (from Colombiana strain) of sera from CCD patients ( Figure 2 B), indicating that the Galα1,2[Galα1,6]Galβ glycotope is likely immunodominant in TcI tGPI-MUC (from Colombiana strain) and less abundant in TcII tGPI-MUC (from Y strain).…”

Section: Resultsmentioning

confidence: 99%

“…In this study, we observed a similar immunoreactivity (no significant difference) to NGP11b and TcI tGPI-MUC (from Colombiana strain) of sera from CCD patients ( Figure 2 B), indicating that the Galα1,2[Galα1,6]Galβ glycotope is likely immunodominant in TcI tGPI-MUC (from Colombiana strain) and less abundant in TcII tGPI-MUC (from Y strain). However, it remains to be confirmed whether tGPI-MUCs from other strains belonging to DTU TcI, prevalent in Northern South America (e.g., Venezuela and Colombia) and Central and North America [ 14 ] would behave similarly regarding seroreactivity in comparison to tGPI-MUCs from other TcII strains. Obviously, an in-depth structural and quantitative analysis of α-Gal-containing O -glycans of tGPI-MUC from both strains and other TcI and TcII strains should be performed in due course.…”

Section: Resultsmentioning

confidence: 99%

“…The diagnosis and treatment of CD can be problematic, owing to the existence of seven discrete typing units (DTUs) or genotypes (TcI-TcVI and Tcbat) with highly diverse ecoepidemiological, geographical, biological, and pathological traits, which result in several different strains that cause different clinical manifestations [ 13 , 14 ]. Currently, only two drugs are available for the chemotherapy of CD, i.e., nifurtimox (NFX) and benznidazole (BNZ).…”

Section: Introductionmentioning

confidence: 99%

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A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease

et al. 2022

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Chagas disease (CD) is caused by the parasite Trypanosoma cruzi and affects 6–7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose O-glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)[Galα(1,6)]Galβ. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease

et al. 2022

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The use of peptides for immunodiagnosis of human Chagas disease

Ribeiro,

Silva,

Lopes

et al. 2024

Amino Acids

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Chagas disease, caused by the protozoa Trypanosoma cruzi, continues to be a serious public health problem in Latin America, worsened by the limitations in its detection. Given the importance of developing new diagnostic methods for this disease, the present review aimed to verify the number of publications dedicated to research on peptides that demonstrate their usefulness in serodiagnosis. To this end, a bibliographic survey was conducted on the PubMed platform using the keyword “peptide” or “epitope” combined with “Chagas disease” or “Trypanosoma cruzi”; “diagno*” or “serodiagnosis” or “immunodiagnosis”, without period restriction. An increasing number of publications on studies employing peptides in ELISA and rapid tests assays was verified, which confirms the expansion of research in this field. It is possible to observe that many of the peptides tested so far originate from proteins widely used in the diagnosis of Chagas, and many of them are part of commercial tests developed. In this sense, as expected, promising results were obtained for several peptides when tested in ELISA, as many of them exhibited sensitivity and specificity values above 90%. Furthermore, some peptides have been tested in several studies, confirming their diagnostic potential. Despite the promising results observed, it is possible to emphasize the need for extensive testing of peptides, using different serological panels, in order to confirm their potential. The importance of producing an effective assay capable of detecting the clinical stages of the disease, as well as new immunogenic antigens that enable new serological diagnostic tools for Chagas disease, is evident.

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Evaluation of the hydroalcoholic extract of Clarisia racemosa as an antiparasitic agent: an in vitro approach

da Cruz Filho,

Duarte,

Marques

et al. 2023

3 Biotech

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Pathogen diversity, immunity, and the fate of infections: lessons learned from Trypanosoma cruzi human–host interactions

Cited by 39 publications

References 100 publications

A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease

A Branched and Double Alpha-Gal-Bearing Synthetic Neoglycoprotein as a Biomarker for Chagas Disease

The use of peptides for immunodiagnosis of human Chagas disease

Evaluation of the hydroalcoholic extract of Clarisia racemosa as an antiparasitic agent: an in vitro approach

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