Article
Biochemistry & Molecular Biology
Teresa Freire, Mercedes Landeira, Cecilia Giacomini, Maria Florencia Festari, Alvaro Pittini, Viviana Cardozo, Alina Brosque, Leticia Monin, Valeria da Costa, Paula Faral-Tello, Carlos Robello, Eduardo Osinaga
Summary: This study found that immunizations with a Trypanosoma cruzi lysate can prevent lung tumor growth and induce anti-tumor immune responses. The induced immunity and tumor protection are associated with the activation of natural killer cells, the production of interferon-gamma, and tumor cell cytotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Priscila Silva Grijo Farani, Khodeza Begum, Glaucia Vilar-Pereira, Isabela Resende Pereira, Igor C. Almeida, Sourav Roy, Joseli Lannes-Vieira, Otacilio Cruz Moreira
Summary: Research explored the immune response-related gene expression changes in heart tissues of C57BL/6 mice chronically infected with T. cruzi and treated with benznidazole (Bz) or Bz+pentoxifylline (PTX). The study found that treatment could mitigate the Th1-driven response in cardiac remodeling processes of CCC patients by restoring the expression of genes related to inflammatory response, cellular development, growth, proliferation, and tissue development pathways.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
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
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
Biochemical Research Methods
P. T. V. Florentino, F. N. L. Vitorino, D. Mendes, J. P. C. da Cunha, C. F. M. Menck
Summary: By using quantitative proteomic analysis, this study revealed the impact of Trypanosoma cruzi infection on the chromatin of host cells. It was discovered that parasites interfere with DNA metabolism during both early and late infection stages. Proteins related to DNA damage repair, oxidative phosphorylation, and vesicle-mediated transport showed increased abundance in the host chromatin. Additionally, the translocation of Apoptosis-inducing Factor to the host cell nucleus after infection suggests that the parasites can induce a programmed cell death known as Parthanatos. These findings contribute to a better understanding of how parasites manipulate the chromatin of host cells to disseminate infection and provide potential targets for future treatments.
JOURNAL OF PROTEOMICS
(2023)
Article
Parasitology
Nestor Anes, Gladys Crisante
Summary: Systematic microscopical observations on tissues from mice show that Trypanosoma cruzi does not exhibit tissue-specific tropism, highlighting its ability to invade various tissues within the mammal host without preference for any particular type.
Article
Immunology
Julian Ernesto Nicolas Gulin, Margarita Maria Catalina Bisio, Daniela Rocco, Jaime Altcheh, Maria Elisa Solana, Facundo Garcia-Bournissen
Summary: This study evaluates the efficacy of Miltefosine (MLT) as a monodrug and combined with benznidazole (BZ) for treating Trypanosoma cruzi infection. MLT showed promising results in inhibiting the parasite in both in vitro and in vivo models, with improved efficacy when combined with BZ. This study provides support for the potential use of MLT in Chagas disease treatment and the exploration of combination therapies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Parasitology
Veronica Olivera, Maria L. Bizai, Evelyn Arias, Santiago Suasnabar, Oscar Bottasso, Ivan Marcipar, Diana Fabbro
Summary: The study found that levels of anti-B13 antibodies in patients who received trypanocidal treatment decreased over time, while untreated patients did not show significant variations. Among untreated patients, ELISA-B13 reactivity was associated with heart involvement.
Article
Immunology
Leyllane Rafael Moreira, Kamila Kassia dos Santos Oliveira, Diego Jose Lira Torres, Michelle da Silva Barros, Tiago Ribeiro de Arruda, Amanda Vasconcelos Nascimento, Ana Karine Araujo Soares, Taciana Mirely Maciel Higino, George Tadeu Nunes Diniz, Valdenia Maria Oliveira Souza, Clarice Neuenschwander Lins de Morais, Virginia Maria Barros de Lorena
Summary: This study evaluated the immune response of peripheral blood mononuclear cells (PBMC) infected in vitro with the Colombian strain (Col) and treated with Benznidazole (Bz). The results showed that Col induced a strong inflammatory response, but from 5 days of infection on, TNF production declined and IL-10 production increased. The Bz treatment did not significantly alter the frequencies of the evaluated cell phenotypes. Therefore, this study highlights the need for strain typing to guide therapy and promote individualized treatment protocols for Chagas disease.
PARASITE IMMUNOLOGY
(2023)
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
Immunology
Marcelo Pires Amaral, Felipe Daniel Cardoso, Ingrid Sancho de Farias, Rafael Queiroz de Souza, Kely Catarine Matteucci, Ana Claudia Torrecilhas, Karina Ramalho Bortoluci
Summary: This study investigated the activation of the NAIP/NLRC4 inflammasome in response to Trypanosoma cruzi infection. The results showed that NAIP and NLRC4 proteins are required for IL-1 beta and NO release in response to T. cruzi infection, and their absence allows for parasite replication in macrophages. Furthermore, Nlrc4 (-/-) and Nlrp3(-/-) macrophages exhibited similar impaired responses to T. cruzi infection, highlighting the non-redundant roles played by these inflammasomes in the context of infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mylla Spirandelli da Costa, Bruna Cristina Borges, Isabella Teixeira Marques, Rayane Cristina de Oliveira, Thaise Lara Teixeira, Julia de Gouveia Santos, Claudio Vieira da Silva
Summary: PClP treatment is non-toxic to both Trypanosoma cruzi and host cells, but inhibits parasite motility, host cell adhesion, and invasion, affecting fundamental processes necessary for a successful T. cruzi infection.
Review
Chemistry, Medicinal
Diogo de Freitas Paiva, Ana Paula dos Santos Matos, Denise de Abreu Garofalo, Tatielle do Nascimento, Mariana Sato de Souza de Bustamante Monteiro, Ralph Santos-Oliveira, Eduardo Ricci-Junior
Summary: Chagas disease, a neglected tropical disease, is caused by a parasitic protozoan and primarily transmitted to humans through vector insects. The traditional drugs for treating the disease have limitations and adverse effects. However, the use of nanocarriers as an alternative treatment has shown promising results in increasing drug stability, selectivity, and efficacy against the parasite.
Article
Immunology
Paulo Gaio, Melisa Gualdron-Lopez, Allysson Cramer, Lisia Esper, Jose Evaldo Rodrigues de Menezes Filho, Jader Santos Cruz, Mauro Martins Teixeira, Fabiana Simao Machado
Summary: This study found that SOCS2 plays a crucial role in regulating the immune response during Trypanosoma cruzi infection and maintaining the balance between inflammatory cells and immune tolerogenic cells.
CLINICAL IMMUNOLOGY
(2022)
Review
Microbiology
Natalia Vacani-Martins, Marcelo Meuser-Batista, Carina de Lima Pereira dos Santos, Alejandro Marcel Hasslocher-Moreno, Andrea Henriques-Pons
Summary: Chagas disease, caused by the protozoan Trypanosoma cruzi, was described over a century ago by Dr. Carlos Chagas in Brazil. Liver involvement, particularly hepatomegaly, is a common clinical sign and is more pronounced in cases of oral infection found in the Amazon region. Despite efforts to understand the mechanisms leading to cardiac and digestive manifestations in chronic patients, the importance of liver involvement and hepatic immune response in disease progression has not received much attention.
Article
Immunology
Leona Gabrysova, Marisol Alvarez-Martinez, Raphaelle Luisier, Luke S. Cox, Jan Sodenkamp, Caroline Hosking, Damian Perez-Mazliah, Charlotte Whicher, Yashaswini Kannan, Krzysztof Potempa, Xuemei Wu, Leena Bhaw, Hagen Wende, Michael H. Sieweke, Greg Elgar, Mark Wilson, James Briscoe, Vicki Metzis, Jean Langhorne, Nicholas M. Luscombe, Anne O'Garra
Article
Infectious Diseases
Damian E. Perez-Mazliah, Melisa D. Castro Eiro, Maria Gabriela Alvarez, Bruno Lococo, Graciela Bertocchi, Gonzalo Cesar, Maria A. Natale, Maria C. Albareda, Rodolfo Viotti, Susana A. Laucella
PLOS NEGLECTED TROPICAL DISEASES
(2018)
Article
Biology
Damian Perez-Mazliah, Peter J. Gardner, Edina Schweighoffer, Sarah McLaughlin, Caroline Hosking, Irene Tumwine, Randall S. Davis, Alexandre J. Potocnik, Victor L. J. Tybulewicz, Jean Langhorne
Correction
Immunology
Leona Gabrysova, Marisol Alvarez-Martinez, Raphaelle Luisier, Luke S. Cox, Jan Sodenkamp, Caroline Hosking, Damian Perez-Mazliah, Charlotte Whicher, Yashaswini Kannan, Krzysztof Potempa, Xuemei Wu, Leena Bhaw, Hagen Wende, Michael H. Sieweke, Greg Elgar, Mark Wilson, James Briscoe, Vicki Metzis, Jean Langhorne, Nicholas M. Luscombe, Anne O'Garra
Review
Microbiology
Michael P. Barrett, Dennis E. Kyle, L. David Sibley, Joshua B. Radke, Rick L. Tarleton
NATURE REVIEWS MICROBIOLOGY
(2019)
Review
Immunology
Damian Perez-Mazliah, Francis M. Ndungu, Racheal Aye, Jean Langhorne
IMMUNOLOGICAL REVIEWS
(2020)
Article
Immunology
Angela D. Pack, Rick L. Tarleton
JOURNAL OF IMMUNOLOGY
(2020)
Review
Immunology
Damian Perez-Mazliah, Alexander I. Ward, Michael D. Lewis
Summary: Trypanosoma cruzi is a versatile parasite that can parasitize almost any nucleated cell type and naturally infects a variety of mammal species, causing Chagas disease. While a large number of people are infected, around two thirds of them remain long-term asymptomatic carriers. Clinical outcomes of chronic infections depend on the interactions between host and parasite.
PARASITE IMMUNOLOGY
(2021)
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)