Article
Immunology
Leonardo Loch, Thiago Souza Onofre, Joao Paulo Ferreira Rodrigues, Nobuko Yoshida
Summary: Metacyclic trypomastigote forms of Trypanosoma cruzi release stage-specific surface molecules gp82 and gp90 to regulate host cell invasion. The release of vesicles by different strains leads to differences in protein profile and the distribution of gp82 and gp90. Treatments like cholesterol-depleting drugs and phospholipase C inhibitors affect the release of these molecules, impacting host cell invasion.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Christian Espinosa-Bustos, Mariana Ortiz Perez, Alonzo Gonzalez-Gonzalez, Ana Maria Zarate, Gildardo Rivera, Javier A. Belmont-Diaz, Emma Saavedra, Mauricio A. Cuellar, Karina Vazquez, Cristian O. Salas
Summary: In this study, a series of new amino naphthoquinone derivatives were synthesized and evaluated for their activity against Trypanosoma cruzi strains. Compounds 2e and 7j showed the lowest IC50 values and 7j exhibited higher activity and selectivity than the reference drug benznidazole. Molecular docking studies revealed that 7j had a good interaction profile on T. cruzi trypanothione reductase (TcTR) and it was predicted to have a favorable pharmacokinetic profile for oral administration.
Article
Multidisciplinary Sciences
Mauro Cesar Cafundo Morais, Diogo Silva, Matheus Marques Milagre, Maykon Tavares de Oliveira, Thais Pereira, Joao Santana Silva, Luciano da F. Costa, Paola Minoprio, Roberto Marcondes Cesar Junior, Ricardo Gazzinelli, Marta de Lana, Helder Nakaya
Summary: In this study, a machine learning approach based on a random forest algorithm was developed for the detection and counting of T. cruzi trypomastigotes in mobile phone images. The method achieved high precision, sensitivity, and area under the ROC curve when tested on a dataset of blood smear samples captured using a mobile device camera. Automating image analysis acquired with a mobile device can reduce costs and improve efficiency in the use of optical microscopes.
Article
Microbiology
Jessica I. de Paula, Eduardo J. Lopes-Torres, Marcelo Jacobs-Lorena, Marcia Cristina Paes, Sung-Jae Cha
Summary: The N3 peptide specifically binds to T. cruzi and inhibits Vero cell infection. Follow-up studies will identify the molecule on the parasite surface to which the N3 peptide binds. This putative T. cruzi ligand may advance chemotherapy design and vaccine development.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Immunology
Ana Carolina Leao, Laila Almeida Viana, Fernanda Fortes de Araujo, Rodrigo de Lourdes Almeida, Leandro Martins Freitas, Anderson Coqueiro-dos-Santos, Denise da Silveira-Lemos, Mariana Santos Cardoso, Joao Luis Reis-Cunha, Andrea Teixeira-Carvalho, Daniella C. Bartholomeu
Summary: Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits high genetic and phenotypic diversity. The MASP family, located on the surface of T. cruzi, is involved in host-parasite interaction. Recombinant MASP proteins were used to investigate their immunogenicity in mice infected with different strains of T. cruzi. Flow cytometry analysis showed changes in MASP recognition profile during infection.
MICROBES AND INFECTION
(2022)
Article
Parasitology
Karolina Ribeiro Goncalves, Ana Lia Mazzeti, Alvaro Fernando da Silva Nascimento, Jessica Mara Castro-Lacerda, Nivia Carolina Nogueira-Paiva, Fernando Augusto Siqueira Mathias, Alexandre Barbosa Reis, Sergio Caldas, Maria Terezinha Bahia
Summary: This study compares the effects of different infection routes via oral and blood infection of Trypanosoma cruzi on mice infection outcomes. Oral infection leads to a wide distribution of the parasite, while blood infection results in higher levels of parasitemia. Oral infection is associated with muscle tissue in the gastrointestinal tract, while blood infection leads to higher inflammation levels.
Article
Biochemistry & Molecular Biology
Alexa Prescilla-Ledezma, Fatima Linares, Mariano Ortega-Munoz, Lissette Retana Moreira, Ana Belen Jodar-Reyes, Fernando Hernandez-Mateo, Francisco Santoyo-Gonzalez, Antonio Osuna
Summary: This study utilizes AFM-based single molecule-force spectroscopy to detect and locate functional trans-sialidases on the surface of extracellular vesicles released by tissue-culture cell-derived trypomastigotes. By engineering AFM cantilevers with functionalized tips bearing anti-TS antibodies, molecular recognition of trans-sialidases using antibody-antigen interaction is achieved. The results demonstrate that the extracellular vesicles isolated from tissue-culture cell-derived trypomastigotes are enriched in trans-sialidases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Thiago Souza Onofre, Joao Paulo Ferreira Rodrigues, Marina Tiemi Shio, Silene Macedo, Maria Aparecida Juliano, Nobuko Yoshida
Summary: The interaction between MT surface molecule gp82 and host cell receptor LAMP2 leads to the activation of phospholipase C, which in turn promotes the activation of PKC and ERK1/2 in the host cell. This cascade of events results in disruption of actin cytoskeleton and lysosome spreading, facilitating the internalization of MT.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Leticia Eligio Garcia, Maria Del Pilar Crisostomo Vazquez, Victor Alberto Maravelez Acosta, Mariana Soria Guerrero, Adrian Cortes Campos, Enedina Jimenez Cardoso
Summary: This study aimed to determine the presence of antigenic proteins of T. cruzi shared with acute lymphoblastic leukemia and neuroblastoma cells. The results contribute to a better understanding of the immune interactions between cancer and parasites, and provide insights for the design of cancer therapies.
Article
Microbiology
Joao Paulo Ferreira Rodrigues, Leonardo Loch, Thiago Souza Onofre, Nobuko Yoshida
Summary: The involvement of NHE1 in the internalization of Trypanosoma cruzi metacyclic trypomastigotes was studied. NHE1 plays a role in maintaining the activation status of diverse protein kinases and preventing inappropriate F-actin arrangement, thus affecting lysosome distribution.
Article
Biochemistry & Molecular Biology
Lissette Retana Moreira, Alexa Prescilla-Ledezma, Alberto Cornet-Gomez, Fatima Linares, Ana Belen Jodar-Reyes, Jorge Fernandez, Ana Karina Ibarrola Vannucci, Luis Miguel De Pablos, Antonio Osuna
Summary: This study characterized the proteomes and nanomechanical properties of extracellular vesicles released by different life stages of Trypanosoma cruzi, the etiologic agent of Chagas disease. The findings revealed significant differences in surface molecular cargos of vesicles between trypomastigotes and epimastigotes, with trypomastigotes exhibiting higher adhesion properties. This suggests a remarkable surface remodeling throughout the parasite's life cycle, potentially impacting the ability of extracellular vesicles to participate in cell communication in diverse infection niches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Eden R. Ferreira, Alexis Bonfim-Melo, Barbara A. Burleigh, Jaime A. Costales, Kevin M. Tyler, Renato A. Mortara
Summary: This study provides the first description of the coordinated mechanism by which T. cruzi escapes from host cells, involving remodeling of the host cell cytoskeleton and rupture of the host cell plasma membrane. The degradation of F-actin by parasite proteases plays a key role in triggering egress, which can be a potential target for novel therapeutic interventions.
Article
Microbiology
Alicia Majeau, Laura Murphy, Claudia Herrera, Eric Dumonteil
Summary: Chagas disease, caused by Trypanosoma cruzi, is an important vector-borne neglected tropical disease with diverse genetic strains that may contribute to poor diagnostic performance. Most markers are suitable for estimating parasite diversity at the DTU level, while some are particularly useful for assessing intra-DTU diversity. Antigenic diversity is likely a key factor in the limited diagnostic performance in Central and North America.
Article
Microbiology
Bruno Souza Bonifacio, Alexis Bonfim-Melo, Renato Arruda Mortara, Eden Ramalho Ferreira
Summary: This study investigates the invasion mechanism of Trypanosoma cruzi and reveals the crucial role of the host cell actin cytoskeleton in the process.
JOURNAL OF EUKARYOTIC MICROBIOLOGY
(2022)
Article
Immunology
Lucia Lopez, Maria Laura Chiribao, Magali C. Girard, Karina A. Gomez, Paula Carasi, Marisa Fernandez, Yolanda Hernandez, Carlos Robello, Teresa Freire, Maria Dolores Pineyro
Summary: The study showed that c-TXNPx induces the recruitment of IL-12/23p40-producing innate antigen-presenting cells and promotes a strong specific Th1 immune response, while c-TXNPxC52S does not. The presence of peroxidatic cysteine is essential for the peroxidase activity and quaternary structure of the protein.
Review
Pharmacology & Pharmacy
Fernanda Lascano, Facundo Garcia Bournissen, Jaime Altcheh
Summary: Chagas disease is a global problem with limited treatment options, highlighting the need for further research on treatment response biomarkers to guide new drug development efforts.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Infectious Diseases
Jaime Altcheh, Luis Castro, Juan C. Dib, Ulrike Grossmann, Erya Huang, Guillermo Moscatelli, Jimy Jose Pinto Rocha, Teresa Estela Ramirez
Summary: Nifurtimox showed good efficacy, safety, and tolerability in treating children with Chagas disease, especially with a 60-day treatment period showing superior serological response. However, the shorter 30-day treatment regimen had lower efficacy compared to the 60-day regimen.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Oncology
Fernanda G. Herrera, Catherine Ronet, Maria Ochoa de Olza, David Barras, Isaac Crespo, Massimo Andreatta, Jesus Corria-Osorio, Aodrenn Spill, Fabrizio Benedetti, Raphael Genolet, Angela Orcurto, Martina Imbimbo, Eleonora Ghisoni, Blanca Navarro Rodrigo, Dominik R. Berthold, Apostolos Sarivalasis, Khalil Zaman, Rafael Duran, Clarisse Dromain, John Prior, Niklaus Schaefer, Jean Bourhis, Georgia Dimopoulou, Zoi Tsourti, Marius Messemaker, Thomas Smith, Sarah E. Warren, Periklis Foukas, Sylvie Rusakiewicz, Mikael J. Pittet, Stefan Zimmermann, Christine Sempoux, Urania Dafni, Alexandre Harari, Lana E. Kandalaft, Santiago J. Carmona, Denarda Dangaj Laniti, Melita Irving, George Coukos
Summary: Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Low-dose radiation reprograms the tumor microenvironment to promote T-cell infiltration and, when combined with immunotherapy, simultaneously mobilizes innate and adaptive immunity, predominantly CD4(+) effector T cells, for tumor control dependent on NKG2D. This combination induces important responses in patients with metastatic immune-cold tumors.
Article
Biochemistry & Molecular Biology
Santiago Bertotti, Ian Fleming, Maria de los Milagros Camara, Camila Centeno Camean, Santiago J. Carmona, Fernan Aguero, Virginia Balouz, Astrid Zahn, Javier M. Di Noia, Juan D. Alfonzo, Carlos A. Buscaglia
Summary: This study identified and characterized the ADAT molecules from the protozoan pathogen Trypanosoma cruzi, and found that they play an important role in tRNA editing and gene expression, revealing differences between parasite and mammalian host tRNA editing and processing.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Massimo Andreatta, Fabrice P. A. David, Christian Iseli, Nicolas Guex, Santiago J. Carmona
Summary: Single-cell transcriptomics enables the study of immune cell heterogeneity at an unprecedented resolution. SPICA, the Swiss portal for immune cell analysis, is a web resource dedicated to exploring and analyzing single-cell RNA-seq data of immune cells, providing curated reference atlases and allowing users to contribute to the database.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
N. Falk, A. J. Berenstein, G. Moscatelli, S. Moroni, N. Gonzalez, G. Ballering, H. Freilij, J. Altcheh
Summary: A retrospective study evaluated the treatment response of a large cohort of children and adults with Chagas disease treated with nifurtimox. The results showed that nifurtimox was highly effective in treating Chagas disease, with patients having excellent treatment responses and resolution of symptoms related to acute Trypanosoma cruzi infection. Clearance of parasitemia and a decrease in T. cruzi antibodies were observed as markers of treatment response. Younger patients showed a higher rate of seroconversion, indicating a more marked treatment response.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemical Research Methods
Massimo Andreatta, Ariel J. Berenstein, Santiago J. Carmona
Summary: scGate is a bioinformatics task in single-cell data analysis that automates the purification of a cell type or cell population of interest. It uses a set of markers to purify the cell population and outperforms other single-cell classifiers. scGate can be applied to multiple modalities of single-cell data and is integrated with the Seurat framework, providing an intuitive tool.
Article
Infectious Diseases
Elias M. Rivera, Guillermo Moscatelli, Griselda Ballering, Agustina Ganuza, Andres M. Alonso, Samanta Moroni, Marina Clemente, Jaime Altcheh, Sergio O. Angel
Summary: The performance of Toxoplasma rGra8, rMic1, and the chimeric rGra4-Gra7 antigens for early congenital toxoplasmosis (CT) diagnosis was evaluated. Sera from CT patients showed high IgG reactivity to rMic1, rGra8, and rGra4-Gra7. The seroreactivity of samples from uninfected infants was lost within 2 months of age.
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
(2022)
Article
Biochemical Research Methods
Mariia Bilous, Loc Tran, Chiara Cianciaruso, Aurelie Gabriel, Hugo Michel, Santiago J. Carmona, Mikael J. Pittet, David Gfeller
Summary: SuperCell is a framework that efficiently combines highly similar cells into metacells, preserving and accelerating the results of single-cell RNA sequencing data analysis.
BMC BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Jana Biermann, Johannes C. Melms, Amit Dipak Amin, Yiping Wang, Lindsay A. Caprio, Alcida Karz, Somnath Tagore, Irving Barrera, Miguel A. Ibarra-Arellano, Massimo Andreatta, Benjamin T. Fullerton, Kristjan H. Gretarsson, Varun Sahu, Vaibhav S. Mangipudy, Trang T. T. Nguyen, Ajay Nair, Meri Rogava, Patricia Ho, Peter D. Koch, Matei Banu, Nelson Humala, Aayushi Mahajan, Zachary H. Walsh, Shivem B. Shah, Daniel H. Vaccaro, Blake Caldwell, Michael Mu, Florian Wuennemann, Margot Chazotte, Simon Berhe, Adrienne M. Luoma, Joseph Driver, Matthew Ingham, Shaheer A. Khan, Suthee Rapisuwon, Craig L. Slingluff, Thomas Eigentler, Martin Roecken, Richard Carvajal, Michael B. Atkins, Michael A. Davies, Albert Agustinus, Samuel F. Bakhoum, Elham Azizi, Markus Siegelin, Chao Lu, Santiago J. Carmona, Hanina Hibshoosh, Antoni Ribas, Peter Canoll, Jeffrey N. Bruce, Wenya Linda Bi, Praveen Agrawal, Denis Schapiro, Eva Hernando, Evan Z. Macosko, Fei Chen, Gary K. Schwartz, Benjamin Izar
Summary: This study provides comprehensive insights into the biology of melanoma brain metastasis (MBM) and reveals the distinct characteristics of cancer cells in MBM, including chromosomal instability and neuronal-like cell state. The study also identifies the presence of monocyte-derived macrophages and dysfunctional T cells in MBM, as well as the geographic differences in cancer immune evasion. These findings contribute to a better understanding of MBM and have implications for future therapeutic exploration.
Article
Biology
Massimo Andreatta, Ariel Tjitropranoto, Zachary Sherman, Michael C. Kelly, Thomas Ciucci, Santiago J. Carmona
Summary: This study utilized single-cell transcriptomics to characterize the diversity of CD4(+) T cells responding to viral infections and built a comprehensive map of their transcriptional states. The research revealed the progressive changes in CD4(+) T cell subtypes during acute infections and identified distinct programs associated with chronic infections. Additionally, the study demonstrated the private nature of virus-specific CD4(+) T cell responses across individuals and their differentiation into Tfh and Th1 subtypes. Moreover, the CD4(+) T cell map developed in this study can be used to interpret cell states in other single-cell datasets.
Article
Microbiology
Jaime Altcheh, Victor Sierra, Teresa Ramirez, Jimy Jose Pinto Rocha, Ulrike Grossmann, Erya Huang, Guillermo Moscatelli, Olivia Ding
Summary: This study confirms the effectiveness and safety of a pediatric formulation of nifurtimox administered in an age- and weight-adjusted regimen for 60 days to treat children with Chagas disease.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Immunology
Jesus Corria-Osorio, Santiago J. J. Carmona, Evangelos Stefanidis, Massimo Andreatta, Yaquelin Ortiz-Miranda, Tania Muller, Ioanna A. A. Rota, Isaac Crespo, Bili Seijo, Wilson Castro, Cristina Jimenez-Luna, Leonardo Scarpellino, Catherine Ronet, Aodrenn Spill, Evripidis Lanitis, Pedro Romero, Sanjiv A. A. Luther, Melita Irving, George Coukos
Summary: Coukos, Corria-Osorio and colleagues have used a genetic engineering approach to improve the effectiveness of CD8(+) T cells in antitumor cell therapy. They engineered these cells to express an IL-2 variant, IL-33 and a programmed cell death protein 1 decoy. The results showed that these engineered cells had enhanced effector functions and were able to overcome exhaustion and control tumors.
Meeting Abstract
Oncology
Johannes C. Melms, Jana Biermann, Amit Dipak Amin, Yiping Wang, Somnath Tagore, Massimo Andreatta, Ajay Nair, Meri Rogava, Patricia Ho, Lindsay A. Caprio, Zachary H. Walsh, Shivem Shah, Daniel H. Vacarro, Blake Caldwell, Adrienne M. Luoma, Joseph Driver, Matthew Ingham, Suthee Rapisuwon, Jennifer Wargo, Craig L. Slinguff, Evan Z. Macosco, Fei Chen, Richard Carvajal, Michael B. Atkins, Michael A. Davies, Elham Azizi, Santiago J. Carmona, Hanina Hibshoosh, Peter D. Canoll, Jeffrey N. Bruce, Wenya L. Bi, Gary K. Schwartz, Benjamin Izar
Article
Cell Biology
Julien Schmidt, Angela R. Smith, Morgane Magnin, Julien Racle, Jason R. Devlin, Sara Bobisse, Julien Cesbron, Victor Bonnet, Santiago J. Carmona, Florian Huber, Giovanni Ciriello, Daniel E. Speiser, Michal Bassani-Sternberg, George Coukos, Brian M. Baker, Alexandre Harari, David Gfeller
Summary: CD8+ T cell recognition of peptide epitopes is crucial in immune responses, but the rules governing which peptides are recognized by T cell receptors remain unclear. Training a predictor called PRIME using recent epitope data improves prediction accuracy, particularly in cancer immunotherapy for identifying new epitopes.
CELL REPORTS MEDICINE
(2021)