Review
Immunology
Concepcion J. Puerta, Adriana Cuellar, Paola Lasso, Jose Mateus, John M. Gonzalez
Summary: Trypanosoma cruzi, the causal agent of Chagas disease, has developed mechanisms of antigenic variability to evade the host immune response. CD8(+) T cells play a key role in chronic Chagas cardiomyopathy, and specific peptide stimulation can activate multifunctional immune responses. Anti-parasitic treatment improves CD8(+) T cell response, and the quality of CD8(+) T cell responses correlates with the outcome of chronic infection. These findings provide valuable resources for discovering new biomarkers, vaccines, and immunotherapy strategies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Immunology
Jose Mateus, Paola Nocua, Paola Lasso, Manuel Carlos Lopez, M. Carmen Thomas, Adriana Egui, Claudia Cuervo, John Mario Gonzalez, Concepcion J. Puerta, Adriana Cuellar
Summary: The study investigates the relationship between parasite control and immune T cell responses in Chagas disease by using distinct infection approaches in an animal model. Different infection outcomes were observed in single or mixed T. cruzi infection with different genotypes, leading to differential immune CD8(+) T cell responses. This suggests that the quality of the CD8(+) T cell response may dictate differences in infection outcomes during chronic T. cruzi infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Rosa Isela Galvez, Thomas Jacobs
Summary: Infection with Trypanosoma cruzi is the most neglected zoonosis in Latin America. CD8(+) T cells play a crucial role in controlling the infection, but cannot eliminate all parasites. Chronic infection leads to dysfunctional CD8(+) T cells with high expression of inhibitory receptor PD-1 and co-expression of transcription factor TOX.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Cristina Gonzalez-Lopez, Wen-Hsiang Chen, Andrea Alfaro-Chacon, Liliana E. Villanueva-Lizama, Miguel Rosado-Vallado, Maria Jesus Ramirez-Sierra, Christian F. Teh-Poot, Jeroen Pollet, Oluwatoyin Asojo, Kathryn M. Jones, Peter J. Hotez, Maria Elena Bottazzi, Julio Vladimir Cruz-Chan
Summary: A therapeutic vaccine containing multiple antigenic epitopes has been developed for Chagas disease, showing promising effects in enhancing cellular immune responses and reducing parasite levels. This study provides a potential strategy for the development of a vaccine candidate for Chagas disease.
Article
Immunology
Fatima Ferragut, Karen M. Cruz, Juan P. Gallardo, Marisa Fernandez, Yolanda Hernandez Vasquez, Karina A. Gomez
Summary: This study focuses on T-cell assays that define the parasite-specificity based on upregulation of TCR stimulation-induced surface markers. The results demonstrate the efficacy of activation-induced markers (AIM) assays in detecting T. cruzi-specific CD4(+) and CD8(+) T cells in chronic Chagas disease patients, using different combinations of surface markers. Additionally, this approach is also successful in identifying the phenotype of activated T lymphocytes based on the expression of CD45RA and CCR7.
Article
Immunology
Livia Silva Araujo Passos, Carolina Cattoni Koh, Luisa Mourao Dias Magalhaes, Maria do Carmo Pereira Nunes, Kenneth John Gollob, Walderez Ornelas Dutra
Summary: DN T cells play a critical role in the cytokine network associated with Chagas heart disease, with IND patients displaying more central memory cells and CARD patients having more effector memory cells. Central memory DN T cells in IND patients show a balanced cytokine profile, while effector memory DN T cells in CARD patients do not. Targeting the activation of effector memory DN T cells may be a potential strategy to control inflammation in Chagas cardiomyopathy and other inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fanny Mathias, Youssef Kabri, Damien Brun, Nicolas Primas, Carole Di Giorgio, Patrice Vanelle
Summary: Chagas disease caused by T. cruzi infection is a major public health problem in Latin America, resulting in 7000 annual deaths. This study synthesized ten new 1-substituted 2-nitropyrrole compounds and evaluated their biological activity. The derivatives showed good selectivity and activity against T. cruzi, but the maximum effect was lower than the reference drug.
Article
Biochemistry & Molecular Biology
Naiara Dutra Barroso Gomes, Emanuel Paula Magalhaes, Lyanna Rodrigues Ribeiro, John Washington Cavalcante, Marcelo Morais Gomes Maia, Felipe Ramon Cunha da Silva, Arif Ali, Marcia Machado Marinho, Emmanuel Silva Marinho, Helcio Silva dos Santos, Alice Maria Costa Martins, Ramon Roseo Paula Pessoa Bezerra de Menezes
Summary: This study evaluated the activity of synthetic p-aminochalcones against T. cruzi and found that they have a trypanocidal effect by causing membrane damage and oxidative stress. Their mechanism of action may be related to inhibition of cruzain and TR.
BIOORGANIC CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Gregorio Guilherme Almeida, Inga Rimkute, Isabela Natalia Pascoal Campos Do Vale, Thomas Liechti, Priscilla Miranda Henriques, Ester Roffe, Fernanda Fortes de Araujo, Manoel Otavio da Costa Rocha, Silvana Maria Eloi Santos, Olindo Assis Martins-Filho, Dragana Jankovic, Alan Sher, Andrea Teixeira-Carvalho, Mario Roederer, Lis Ribeiro do Valle Antonelli
Summary: In this study, high-dimensional flow cytometry was used to evaluate CD4(+) T cells in patients with different clinical forms. The results showed that activated CD4(+) T cells were increased in patients, while functional regulatory T cells were reduced. These findings provide evidence for the involvement of these cells in the development of Chagas cardiomyopathy and their potential as biomarkers for disease progression.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Juliana Magalhaes Chaves Barbosa, Yasmin Pedra-Rezende, Luiza Dantas Pereira, Tatiana Galvao de Melo, Helene Santos Barbosa, Joseli Lannes-Vieira, Solange Lisboa de Castro, Anissa Daliry, Kelly Salomao
Summary: The combination treatment of Bz + AMD can attenuate the damage caused by T. cruzi infection in cardiac cells and have a certain control effect on parasite replication.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Augusto L. dos Santos, Maiara Amaral, Flavia Rie Hasegawa, Joao Henrique G. Lago, Andre G. Tempone, Patricia Sartorelli
Summary: The sesquiterpene T-cadinol from Casearia sylvestris shows promising activity against Trypanosoma cruzi, with potential mitochondrial impairment leading to hyperpolarization of the membrane potential. Further optimization and study of this compound for Chagas disease drug discovery is warranted.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Maria Carmo P. Nunes, Lewis F. Buss, Jose Luiz P. Silva, Larissa Natany A. Martins, Claudia Di Lorenzo Oliveira, Clareci Silva Cardoso, Bruno Oliveira de Figueiredo Brito, Ariela Mota Ferreira, Lea Campos Oliveira, Ana Luiza Bierrenbach, Fabio Fernandes, Michael P. Busch, Viviane Tiemi Hotta, Luiz Mario Baptista Martinelli, Maria Carolina F. Almeida Soeiro, Adriana Brentegani, Vera M. C. Salemi, Marcia M. Menezes, Antonio Luiz P. Ribeiro, Ester Cerdeira Sabino
Summary: This study provides a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population, highlighting the central importance of anti-T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.
Article
Immunology
Marianne Rocha-Hasler, Gabriel Melo de Oliveira, Aline Nefertiti da Gama, Ludmila Ferreira de Almeida Fiuza, Anna Frieda Fesser, Monica Cal, Romina Rocchetti, Raiza Brandao Peres, Xue Li Guan, Marcel Kaiser, Maria de Nazare Correia Soeiro, Pascal Maser
Summary: The study found that treatment with posaconazole alone in chronic Chagas disease patients resulted in a high relapse rate, prompting the search for suitable combination partners such as inhibitors of sterol and sphingolipid biosynthetic enzymes. In vitro and in vivo experiments revealed that the combination of tomatidine (TH) with posaconazole showed synergistic effects against Trypanosoma cruzi, indicating a potential for improved treatment outcomes.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Sergio Castaneda, Marina Munoz, Peter J. Hotez, Maria Elena Bottazzi, Alberto E. Paniz-Mondolfi, Kathryn M. Jones, Rojelio Mejia, Cristina Poveda, Juan David Ramirez
Summary: Chagas disease is caused by Trypanosoma cruzi and has a profound impact on the gastrointestinal tract. Alterations in the gut microbiome caused by the parasite may play a crucial role in host-parasite interactions and immune responses. Understanding this interaction could provide valuable insights into the pathophysiology of the disease and the development of new treatments.
MICROBIOLOGY SPECTRUM
(2023)
Article
Immunology
Maria Cristina Vanrell, Santiago Jose Martinez, Lucila Ibel Munoz, Betiana Nebai Salassa, Julian Gambarte Tudela, Patricia Silvia Romano
Summary: In this study, ursolic acid (UA) was found to reduce Trypanosoma cruzi infection in vitro by decreasing the number of intracellular amastigotes through the induction of autophagy. UA also induced autophagy response in both macrophages and cardiac cells, and inhibition of this pathway restored the level of infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
D. Brent Weatherly, Duo Peng, Rick L. Tarleton
Correction
Biochemistry & Molecular Biology
Dilrukshi K. Ekanayake, Todd Minning, Brent Weatherly, Kapila Gunasekera, Daniel Nilsson, Rick Tarleton, Torsten Ochsenreiter, Robert Sabatini
MOLECULAR AND CELLULAR BIOLOGY
(2017)
Article
Immunology
Melisa D. Castro Eiro, Maria G. Alvarez, Gretchen Cooley, Rodolfo J. Viotti, Graciela L. Bertocchi, Bruno Lococo, Maria C. Albareda, Ana M. De Rissio, Mar-A A. Natale, Cecilia Parodi, Rick L. Tarleton, Susana A. Laucella
FRONTIERS IN IMMUNOLOGY
(2017)
Article
Biology
Fernando J. Sanchez-Valdez, Angel Padilla, Wei Wang, Dylan Orr, Rick L. Tarleton
Article
Immunology
Maria C. Albareda, Maria A. Natale, Ana M. De Rissio, Marisa Fernandez, Alicia Serjan, Maria G. Alvarez, Gretchen Cooley, Huifeng Shen, Rodolfo Viotti, Jacqueline Bua, Melisa D. Castro Eiro, Myriam Nunez, Laura E. Fichera, Bruno Lococo, Karenina Scollo, Rick L. Tarleton, Susana A. Laucella
FRONTIERS IN IMMUNOLOGY
(2018)
Article
Microbiology
Angela D. Pack, Matthew H. Collins, Charles S. Rosenberg, Rick L. Tarleton
Review
Microbiology
Michael P. Barrett, Dennis E. Kyle, L. David Sibley, Joshua B. Radke, Rick L. Tarleton
NATURE REVIEWS MICROBIOLOGY
(2019)
Article
Immunology
Angela D. Pack, Rick L. Tarleton
JOURNAL OF IMMUNOLOGY
(2020)
Article
Microbiology
Wei Wang, Duo Peng, Rodrigo P. Baptista, Yiran Li, Jessica C. Kissinger, Rick L. Tarleton
Summary: The protozoan Trypanosoma cruzi establishes life-long infections in humans and other mammals due to the genetic diversity in genes encoding target antigens, which allows the parasite to evade immune responses. This diversity is maintained through processes like gene amplification and recombination, leading to extreme genome flexibility. This poses challenges for developing protective vaccines and contributes to the species-specific biological diversity of T. cruzi.
Article
Infectious Diseases
Angel M. Padilla, Phil Y. Yao, Tre J. Landry, Gretchen M. Cooley, Susan M. Mahaney, Isabela Ribeiro, John L. VandeBerg, Rick L. Tarleton
Summary: The study demonstrates the complexity of infection dynamics, parasite phenotypes, and immune response patterns that can occur in a primate group, despite being housed in a uniform environment at a single location, and the limited time period over which the T. cruzi infections were established.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Immunology
Rick L. Tarleton
Summary: Human clinical trials are costly and failures can discourage future attempts. Chagas disease drug discovery efforts have faced numerous trial failures. Guidelines specific to Chagas disease and other neglected tropical diseases can help avoid these failures by addressing challenges and utilizing advantages such as multi-species natural infection systems.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Immunology
Molly E. Bunkofske, Natasha Perumal, Brooke White, Eva-Maria Strauch, Rick Tarleton
Summary: Infection with Trypanosoma cruzi induces CD8+ T cell responses targeting epitopes in the large trans-sialidase (TS) gene family, but these responses are not essential for immune control. A screen for alternative CD8+ T cell targets identified a previously uncharacterized epitope, MUCKb25, within mucin family proteins. However, the MUCKb25-specific response was dispensable for infection control and vaccination to generate MUCK-specific CD8+ T cells failed to confer protection. These findings highlight the limited effector potential of CD8+ T cells in T. cruzi-infected mice. Journal of Immunology, 2023, 210: 420-430.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Microbiology
Juan M. Bustamante, Brooke E. White, Gregory K. Wilkerson, Carolyn L. Hodo, Lisa D. Auckland, Wei Wang, Stephanie McCain, Sarah A. Hamer, Ashley B. Saunders, Rick L. Tarleton
Summary: This study demonstrates that higher dose, intermittent administration of benznidazole can effectively treat Trypanosoma cruzi infection. Administration twice a week, for more than 4 months, provides the best chance for parasitological cure.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Editorial Material
Parasitology
Rick L. Tarleton
Summary: The author and his colleagues have recently reported on a benzoxaborole compound that can consistently cure parasites in experimentally infected mice and naturally infected non-human primates (NHPs). Although these results do not guarantee success in human clinical trials, they significantly reduce the risks and provide strong justification for such trials. Effective drug discovery relies on understanding host and parasite biology and expertise in designing and validating chemical entities. This opinion piece aims to provide insights into the process that led to the discovery of AN15368, hoping to facilitate the discovery of more clinical candidates for Chagas disease.
TRENDS IN PARASITOLOGY
(2023)
Article
Cell Biology
Juan M. Bustamante, Fernando Sanchez-Valdez, Angel M. Padilla, Brooke White, Wei Wang, Rick L. Tarleton
SCIENCE TRANSLATIONAL MEDICINE
(2020)