Article
Parasitology
Flavia de Souza Marques, Thays Helena Chaves Duarte, Viviane Flores Xavier, Aline Tonhela Ferraz, Aline Coelho das Merces, Thais Vieira Carvalho Silva, Livia Carvalho Mendes, Luciana da Fonseca Medeiros, Luisa Perin, Fernando Augusto Siqueira Mathias, Katia da Silva Fonseca, Nivia Carolina Nogueira-Paiva, Claudia Martins Carneiro, Paula Melo de Abreu Vieira
Summary: Through experimentation, it was found that mice infected with MT forms had lower survival rates and higher tissue parasitism in the acute phase, which was associated with an exacerbated activation of the immune system. These results highlight the importance of the inoculum source and strain, as different forms of different strains appear to promote distinct diseases.
PARASITOLOGY RESEARCH
(2021)
Article
Immunology
Brenda Celeste Gutierrez, Estela Lammel, Stella Maris Gonzalez-Cappa, Carolina Veronica Poncini
Summary: The study reveals that the two infective stages of T. cruzi (metacyclic or blood trypomastigotes) induce different immune responses in the body. Animals inoculated with metacyclic forms show better survival rates and lower parasite load, while those injected with blood trypomastigotes exhibit higher mortality and parasite load.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Pauline Brochet, Barbara Ianni, Joao P. S. Nunes, Amanda F. Frade, Priscila C. Teixeira, Charles Mady, Ludmila R. P. Ferreira, Andreia Kuramoto, Cristina W. Pissetti, Bruno Saba, Darlan D. S. Candido, Fabricio Dias, Marcelo Sampaio, Jose A. Marin-Neto, Abilio Fragata, Ricardo C. F. Zaniratto, Sergio Siqueira, Giselle D. L. Peixoto, Vagner O. C. Rigaud, Paula Buck, Rafael R. Almeida, Hui Tzu Lin-Wang, Andre Schmidt, Martino Martinelli, Mario H. Hirata, Eduardo Donadi, Virmondes Rodrigues Junior, Alexandre C. Pereira, Jorge Kalil, Lionel Spinelli, Edecio Cunha-Neto, Christophe Chevillard
Summary: This study proposes two sets of DNA methylation biomarkers that can predict the occurrence and stage of Chagas disease cardiomyopathy. Using machine learning algorithms, predictions in a test cohort achieved an accuracy of over 95%. These biomarkers are also associated with immune response, nervous system, ion transport, and ATP synthesis pathways.
FRONTIERS IN IMMUNOLOGY
(2022)
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
Clinical Neurology
Wouter Peelaerts, Gabriela Mercado, Sonia George, Marie Villumsen, Alysa Kasen, Miguel Aguileta, Christian Linstow, Alexandra B. Sutter, Emily Kuhn, Lucas Stetzik, Rachel Sheridan, Liza Bergkvist, Lindsay Meyerdirk, Allison Lindqvist, Martha L. Escobar Gavis, Chris van den Haute, Scott J. Hultgren, Veerle Baekelandt, J. Andrew Pospisilik, Tomasz Brudek, Susana Aznar, Jennifer A. Steiner, Michael X. Henderson, Lena Brundin, Magdalena I. Ivanova, Tom J. Hannan, Patrik Brundin
Summary: Symptoms in the urogenital organs are common in MSA, and our study suggests that infection of the genitourinary tract could trigger alphaSyn aggregation, leading to MSA diagnosis. Urinary tract infections are associated with future MSA diagnosis and impact both men and women. Bacterial infection of the urinary bladder triggers synucleinopathy in mice, indicating a potential link between bacterial infections and MSA.
ACTA NEUROPATHOLOGICA
(2023)
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
Biochemistry & Molecular Biology
Luca Magistrelli, Elena Contaldi, Francesca Vignaroli, Silvia Gallo, Federico Colombatto, Roberto Cantello, Cristoforo Comi
Summary: Parkinson's disease is a neurodegenerative disease characterized by loss of dopaminergic neurons. Recent studies have shown that immune system hyperactivation and production of pro-inflammatory cytokines are signature features of idiopathic Parkinson's disease. Genetic factors may also play a role in some patients.
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
Multidisciplinary Sciences
Toshiki Nagakubo, Yuhei O. Tahara, Makoto Miyata, Nobuhiko Nomura, Masanori Toyofuku
Summary: The study utilized super-resolution live-cell imaging and biochemical analysis to reveal that Corynebacterium glutamicum forms different types of bacterial membrane vesicles (MVs) via different routes in response to environmental conditions. DNA-damaging stress and envelope stress induced MV formation through distinct mechanisms, which were found to be conserved in other mycolic acid-containing bacteria. This research provides insights into how the complex cell envelope structure intrinsically generates various types of MVs in single cell organisms.
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
Oncology
Chaoran Zang, Yan Zhao, Ling Qin, Guihai Liu, Jianping Sun, Kang Li, Yanan Zhao, Shoupeng Sheng, Honghai Zhang, Ning He, Peng Zhao, Qi Wang, Xi Li, Yanchun Peng, Tao Dong, Yonghong Zhang
Summary: The study revealed specific T cell responses against CTAs and TAAs in HCC patients. In early-stage HCC patients, SALL4-specific response was the most prominent, followed by MAGE-A3, NY-ESO-1, MAGE-A1, and SSX2. The protective role of CTA-specific responses was suggested for one-year recurrence-free survival after treatment. As HCC progressed, CTA and SALL4-specific T cell responses decreased while AFP-specific response increased, indicating the potential of immunotherapy at an early stage of HCC.
Article
Cell Biology
Radouane Ouali, Larissa Rezende Vieira, Didier Salmon, Sabrina Bousbata
Summary: Understanding the immune physiology of Rhodnius prolixus, a major Chagas disease vector, through the characterization of its hemolymph proteome provides new insights into triatomine immunology. The study reveals that Trypanosoma cruzi triggers an early systemic immune response in the hemolymph, leading to the activation of various immune proteins and the overexpression of specific proteins. Additionally, novel proteins with immune properties, such as the putative c1q-like protein and the immunoglobulin I-set domain-containing protein, have been identified. The findings contribute to a better understanding of the host-parasite interaction and pave the way for the development of new strategies to control vector populations and pathogen transmission.
Article
Immunology
Theo G. M. Oliveira, Gabriela Venturini, Juliana M. Alvim, Larissa L. Feijo, Carla L. Dinardo, Ester C. Sabino, Jonathan G. Seidman, Christine E. Seidman, Jose E. Krieger, Alexandre C. Pereira
Summary: This study used hiPSC-CM to investigate the patterns of infection, proliferation, and transcriptional response in IND and CCC patients. The results showed no significant difference in T. cruzi infection and proliferation efficiency between IND and CCC patients. However, there were significant differences in the transcriptional response to the parasite in hiPSC-CM from IND and CCC patients. IND hiPSC-CM showed differences in the expression of genes related to antigen processing and presentation, while CCC hiPSC-CM showed increased expression of genes associated with the mTORC1 pathway and unfolded protein response. These findings suggest that baseline genetic differences may have an impact on the development of chronic outcomes and the presentation of cardiac symptoms.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Cell Biology
Huihui Li, Mingzhi Zhang, Quanyi Zhao, Wanqing Zhao, Yan Zhuang, Jin Wang, Weijian Hang, Zheng Wen, Li Wang, Chen Chen, Dao Wen Wang
Summary: This study reveals the pathogenesis of fulminant myocarditis (FM) and suggests potential therapeutic strategies. Healthy cardiomyocytes lose their function and differentiate into pro-angiogenic and pro-inflammatory cells in FM. Neutrophils, after migrating to the heart, continuously attract peripheral neutrophils via specific signals, resulting in their acute accumulation in the heart. Moreover, neutrophils can amplify the inflammatory response by recruiting and activating pro-inflammatory cells. Blockade of the self-recruiting loop of neutrophils substantially alleviates FM in mice.
Article
Cardiac & Cardiovascular Systems
Bruna F. Pinto, Nayara I. Medeiros, Andrea Teixeira-Carvalho, Jacqueline A. Fiuza, Silvana M. Eloi-Santos, Maria C. P. Nunes, Silvana A. Silva, Tereza C. M. Fontes-Cal, Mayara Belchior-Bezerra, Walderez O. Dutra, Rodrigo Correa-Oliveira, Juliana A. S. Gomes
Summary: Chagas cardiomyopathy is a symptomatic cardiac form of Chagas disease, characterized by fibrosis of the heart muscle. The activation of T lymphocyte subsets is regulated by CD80 and CD86 co-stimulatory molecules, and their involvement in the development of Chagas cardiomyopathy has been identified.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Fernanda Fortes de Araujo, Matheus Fernandes Costa-Silva, Agnes Antonia Sampaio Pereira, Felipe Dutra Rego, Victoria Hellena Silva Pereira, Jaqueline Paulino de Souza, Luana Oliveira Borges Fernandes, Olindo Assis Martins-Filho, Celia Maria Ferreira Gontijo, Vanessa Peruhype-Magalhaes, Andrea Teixeira-Carvalho
Summary: Interactions between pathogens and host immune responses are critical for immunity and pathology against Leishmania parasites. Proinflammatory responses enhance immune control, while anti-inflammatory responses favor parasite proliferation. Chemokines play a key role in determining cellular composition at inflammatory sites.
Article
Engineering, Multidisciplinary
Alan M. Braga, Regis C. P. Marques, Fatima N. S. Medeiros, Jeova F. S. Rocha Neto, Andrea G. C. Bianchi, Claudia M. Carneiro, Daniela M. Ushizima
Summary: This paper introduces a novel hierarchical nuclei segmentation algorithm based on narrow band level set implementation, which achieved significant accuracy and Dice coefficient values in the segmentation of cervical cell images, and demonstrated high average accuracy in classification experiments. The results indicate the suitability of the algorithm for integration into decision support systems for cervical cell screening.
Article
Medicine, Research & Experimental
Carolina D'Avila-Mesquita, Ariel E. S. Couto, Ligia C. B. Campos, Tauana F. Vasconcelos, Jessyca Michelon-Barbosa, Carlos A. C. Corsi, Fabiola Mestriner, Bruno C. Petroski-Moraes, Maria J. Garbellini-Diab, Daniel M. S. Couto, Maria C. Jordani, Denise Ferro, Lourenco Sbragia, Edwaldo E. Joviliano, Paulo R. Evora, Rodrigo de Carvalho Santana, Olindo Assis Martins-Filho, Katarzyna Polonis, Mayra G. Menegueti, Mauricio S. Ribeiro, Maria Auxiliadora-Martins, Christiane Becari
Summary: The study revealed that plasma levels of MMP-2 and MMP-9 in COVID-19 patients were associated with clinical outcomes and mortality. MMP-9 levels in COVID-19 patients were influenced by comorbidities such as hypertension and obesity, while MMP-2 levels were affected by hypertension.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Parasitology
Livia Mendes Carvalho, Miria Rodrigues Gusmao, Ana Flavia Pereira Costa, Rory Cristiane Fortes de Brito, Rodrigo Dian de Oliveira Aguiar-Soares, Jamille Mirelle de Oliveira Cardoso, Alexandre Barbosa Reis, Claudia Martins Carneiro, Bruno Mendes Roatt
Summary: The immunochemotherapy using miltefosine along with LBSapMPL-vaccine showed promising results in controlling Leishmania infection and upregulating immunity, suggesting it as a potential alternative option for human and canine visceral leishmaniasis.
Article
Multidisciplinary Sciences
Maria A. Duque-Correa, David Goulding, Faye H. Rodgers, Claire Cormie, Kate Rawlinson, J. Andrew Gillis, Allison J. Bancroft, Hayley M. Bennett, Magda Lotkowska, Adam J. Reid, Anneliese Speak, Paul Scott, Nicholas Redshaw, Catherine McCarthy, Cordelia Brandt, Catherine Sharpe, Caroline Ridley, Judit Gali Moya, Claudia M. Carneiro, Tobias Starborg, Kelly S. Hayes, Nancy Holroyd, Mandy Sanders, David J. Thornton, Richard K. Grencis, Matthew Berriman
Summary: Whipworms are large parasites causing chronic disease in humans and other mammals. Researchers have discovered how the larvae invade host epithelial cells, establishing infection by degrading mucus layers and creating tunnels. This interaction between the whipworm and the host triggers an immune response and tissue repair.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Alcides Castro e Silva, Americo Tristao Bernardes, Eduardo Augusto Goncalves Barbosa, Igor Aparecido Santana das Chagas, Wesley Dattilo, Alexandre Barbosa Reis, Servio Pontes Ribeiro
Summary: This article studies a version of the SIR model that takes into account the spatial localization, movement, and social isolation probabilities of individuals. The effects of virus variants and vaccination rates on pandemic dynamics are discussed. The study shows that continuous waves of infections will occur unless global vaccination is implemented.
Article
Multidisciplinary Sciences
Olivia J. S. Macleod, Alexander D. Cook, Helena Webb, Mandy Crow, Roisin Burns, Maria Redpath, Stefanie Seisenberger, Camilla E. Trevor, Lori Peacock, Angela Schwede, Nicola Kimblin, Amanda F. Francisco, Julia Pepperl, Steve Rust, Paul Voorheis, Wendy Gibson, Martin C. Taylor, Matthew K. Higgins, Mark Carrington
Summary: The study reveals that ISG65 of T. brucei functions as a receptor for complement component 3 and plays a role in reducing trypanosome susceptibility to C3-mediated clearance. This finding provides important insights into the interaction between trypanosomes and the innate immune system.
NATURE COMMUNICATIONS
(2022)
Article
Infectious Diseases
Amanda Fortes Francisco, Ursula Saade, Shiromani Jayawardhana, Hans Pottel, Ivan Scandale, Eric Chatelain, Peter Liehl, John M. Kelly, Maan Zrein
Summary: This study evaluated serological procedures for the diagnosis of T. cruzi infections and confirmation of parasitological cure using an experimental mouse model. The researchers identified a set of antigens that provide a rapid and accurate read-out of both acute and chronic T. cruzi infection. They also discovered specific antibody responses that can be correlated with parasite reduction or persistent infection. These findings could be used to develop diagnostic techniques and biomarkers for monitoring the efficacy of anti-T. cruzi drug treatment in a clinical setting.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Chemistry, Medicinal
Taisuke Tawaraishi, Atsuko Ochida, Yuichiro Akao, Sachiko Itono, Masahiro Kamaura, Thamina Akther, Mitsuyuki Shimada, Stacie Canan, Sanjoy Chowdhury, Yafeng Cao, Kevin Condroski, Ola Engkvist, Amanda Francisco, Sunil Ghosh, Rina Kaki, John M. Kelly, Chiaki Kimura, Thierry Kogej, Kazuya Nagaoka, Akira Naito, Garry Pairaudeau, Constantin Radu, Ieuan Roberts, David Shum, Nao-aki Watanabe, Huanxu Xie, Shuji Yonezawa, Osamu Yoshida, Ryu Yoshida, Charles Mowbray, Benjamin Perry
Summary: Probing multiple proprietary pharmaceutical libraries in parallel through virtual screening led to the rapid expansion of structure-activity relationship (SAR) around hit compounds with moderate efficacy against Trypanosoma cruzi. The SAR was further developed through a potency-improving scaffold hop and design guided by phenotypic virtual screening, resulting in the identification of two promising hit compounds 54 and 85. Compound 85 showed a significant reduction in parasitemia in an in vivo model, confirming its potential as an anti-trypanosome treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Fernando Augusto Siqueira Mathias, Thais Lopes Valentim Di Paschoale Ostolin, Levi Eduardo Soares Reis, Jamille Mirelle de Oliveira Cardoso, Rory Cristiane Fortes De Brito, Rodrigo Dian de Oliveira Aguiar Soares, Bruno Mendes Roatt, Paula Melo de Abreu Vieira, Alexandre Barbosa Reis
Summary: This study evaluated the effect and optimal dose of adjuvant systems for a vaccine candidate against Leishmania (Viannia) braziliensis. The combination of saponin and monophosphoryl lipid A (SM) as an adjuvant system increased the production of TNF and IFN-gamma, leading to the generation of central and effector memory CD4(+) T cells. Therefore, using an adjuvant system can enhance the innate immune response and has the potential for future vaccine development.
Article
Chemistry, Medicinal
Livio Racane, Lucija Pticek, Sanja Kostrun, Silvana Raic-Malic, Martin Craig Taylor, Michael Delves, Sam Alsford, Francisco Olmo, Amanda Fortes Francisco, John M. Kelly
Summary: We designed and synthesized a series of symmetric benzothiazole derivatives and evaluated their efficacy against Trypanosoma brucei and Plasmodium falciparum. One compound showed high selectivity and trypanocidal activity, curing mice infected with trypanosomiasis. It also exhibited activity against the malaria parasite.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Srinivasa P. S. Rao, Matthew K. Gould, Jonas Noeske, Manuel Saldivia, Rajiv S. Jumani, Pearly S. Ng, Olivier Rene, Yen-Liang Chen, Marcel Kaiser, Ryan Ritchie, Amanda Fortes Francisco, Nila Johnson, Debjani Patra, Harry Cheung, Colin Deniston, Andreas D. Schenk, Wilian A. Cortopassi, Remo S. Schmidt, Natalie Wiedemar, Bryanna Thomas, Rima Palkar, Nahdiyah A. Ghafar, Vanessa Manoharan, Catherine Luu, Jonathan E. Gable, Kah Fei Wan, Elmarie Myburgh, Jeremy C. Mottram, Whitney Barnes, John Walker, Charles Wartchow, Natasha Aziz, Colin Osborne, Juergen Wagner, Christopher Sarko, John M. Kelly, Ujjini H. Manjunatha, Pascal Maeser, Jan Jiricek, Suresh B. Lakshminarayana, Michael P. Barrett, Thierry T. Diagana
Summary: Millions of people in Latin America and sub-Saharan Africa are at risk of trypanosomatid infections. Researchers have identified a class of cyanotriazoles (CTs) that have potent trypanocidal activity and can potentially be used for the treatment of Chagas disease and human African trypanosomiasis. These CT compounds act by selectively and irreversibly inhibiting trypanosomal topoisomerase II and stabilizing DNA:enzyme cleavage complexes.
Article
Microbiology
Amanda Fortes Francisco, Giovane R. Sousa, Mhairi Vaughan, Harry Langston, Archie Khan, Shiromani Jayawardhana, Martin C. Taylor, Michael D. Lewis, John M. Kelly
Summary: This study demonstrates the potential of the C3H/HeN:JR host:parasite combination as an experimental model for Chronic Chagas cardiomyopathy (CCC). The model exhibited cardiac abnormalities and inflammation, and could be used for screening new compounds and drugs to prevent or alleviate CCC development.
Article
Chemistry, Medicinal
Chee Wei Ang, Brendon M. Lee, Colin J. Jackson, Yuehong Wang, Scott G. Franzblau, Amanda F. Francisco, John M. Kelly, Paul Bernhardt, Lendl Tan, Nicholas P. West, Melissa L. Sykes, Alexandra O. Hinton, Raghu Bolisetti, Vicky M. Avery, Matthew A. Cooper, Mark A. T. Blaskovich
Summary: Tuberculosis and parasitic infections pose a significant threat to public health and economic growth worldwide. This study explores a new subclass of bicyclic nitroimidazole compounds and their potential as treatments for tuberculosis and Chagas disease, demonstrating promising results in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Letter
Parasitology
Servio Pontes Ribeiro, Mariana Moncassin Vale, Jose Alexandre Felizola Diniz-Filho, Geraldo Wilson Fernandes, Alexandre Barbosa Reis, Carlos Eduardo de Viveiros Grelle
REVISTA DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL
(2022)