Review
Immunology
Junli Li, Lingjun Zhan, Chuan Qin
Summary: BCG vaccine, proven to be effective against tuberculosis, also shows non-specific protective effects against various diseases. The recent COVID-19 outbreak has brought BCG vaccine, a classic vaccine, back into the spotlight, prompting further research into its specific and non-specific protection mechanisms.
Article
Biochemistry & Molecular Biology
Boli Ma, Xueyi Nie, Lei Liu, Mengyuan Li, Qi Chen, Yueyang Liu, Yuxin Hou, Yi Yang, Jinrui Xu
Summary: The inhibition of PERK alleviated pyroptosis induced by BCG infection, showing an effect of resistance against infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Emmelie Eckhardt, Jan Schinkoethe, Marcel Gischke, Julia Sehl-Ewert, Bjorn Corleis, Anca Dorhoi, Jens Teifke, Dirk Albrecht, Annemieke Geluk, Martine Gilleron, Max Bastian
Summary: The study demonstrates the significant role of CD1b-restricted DURTs in immune control of Mycobacterium tuberculosis and suggests that the PIM6 vaccine can reduce pathology and bacterial load after infection.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Lei Zhang, Yuqing Li, Lingli Zhou, Houhong Zhou, Liefu Ye, Tong Ou, Huaishan Hong, Shiwen Zheng, Ziyu Zhou, Kang Wu, Zeqin Yan, Jean Paul Thiery, Jun Cui, Song Wu
Summary: YTHDF2 is upregulated in bladder cancer and promotes tumor growth by inhibiting RIG-I-mediated immune signaling, highlighting the significance of m(6)A modifications in bladder cancer and providing therapeutic opportunities.
Article
Immunology
Reginaldo G. Bastos, Heba F. Alzan, Vignesh A. Rathinasamy, Brian M. Cooke, Odir A. Dellagostin, Raul G. Barletta, Carlos E. Suarez
Summary: This article discusses the potential use of BCG TI as a strategy to control babesiosis infection more efficiently, supported by experimental evidence and the possibility of vaccine development.
Review
Chemistry, Multidisciplinary
Mira Holzheimer, Jeffrey Buter, Adriaan J. Minnaard
Summary: The pathogen Mycobacterium tuberculosis has a thick cell envelope rich in Mtb-specific lipids, glycolipids, and glycans, which are directly involved in host-pathogen interactions, intracellular survival, and virulence. Synthesizing these components aids in studying Mtb immunology and has driven advancements in the field of organic synthesis.
Article
Immunology
Huanhuan Ning, Jian Kang, Yanzhi Lu, Xuan Liang, Jie Zhou, Rui Ren, Shan Zhou, Yong Zhao, Yanling Xie, Lu Bai, Linna Zhang, Yali Kang, Xiaojing Gao, Mingze Xu, Yanling Ma, Fanglin Zhang, Yinlan Bai
Summary: In this study, researchers constructed a recombinant BCG vaccine (rBCG-DisA) with di-adenylate cyclase (DisA) and found that it induced enhanced immune responses in mice, leading to trained immunity and adaptive immunity. Additionally, rBCG-DisA showed promising potential in protecting against M. tuberculosis infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Maria A. Duarte C., Jeismar M. Carballo O., Yetsenia M. De Gouveia, Angie Garcia, Diana Ruiz, Teresa Gledhill, Eglys Gonzalez-Marcano, Ana F. Convit
Summary: ConvitVax is a personalized vaccine for breast cancer treatment, which has been shown to be safe and effective in preclinical studies on BALB/c mice.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Emilie Jalbert, Cuining Liu, Vidya Mave, Nancy Lang, Anju Kagal, Chhaya Valvi, Mandar Paradkar, Nikhil Gupte, Rahul Lokhande, Renu Bharadwaj, Vandana Kulkarni, Amita Gupta, Adriana Weinberg
Summary: There is a need for more effective vaccines against tuberculosis (TB) than the currently licensed BCG vaccine. This study aimed to identify new vaccine benchmarks by examining immune responses in individuals able to eradicate the infection (TB-resisters) and individuals with latent infection (LTBI-participants). Results showed that TB-resisters had higher frequencies of certain T cells and higher proportions of polyfunctional T cells expressing specific markers, while LTBI-participants had higher expression of activation markers and cytokines. The findings suggest that specific T cell responses may be desirable for new TB vaccines.
Review
Medicine, Research & Experimental
Benjamin N. Koleske, William R. Jacobs, William R. Bishai
Summary: The complete genome sequence of Mycobacterium tuberculosis, achieved in 1998, has provided invaluable insights and tools for understanding tuberculosis. Whole-genome sequencing has improved our ability to predict antibacterial susceptibility and track epidemics. It also helps in studying the effectiveness of TB vaccines and identifying targets for new treatments.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Chemistry, Applied
Zhijun Song, Yu Liu, Jieyu Gao, Jiansen Hu, Hongtao He, Shengwang Dai, Luoqiang Wang, Huanqin Dai, Lixin Zhang, Fuhang Song
Summary: During the systematic screening of bioactive compounds, a marine-derived fungus strain exhibited moderate bioactivities against several bacteria. Further chemical investigation led to the discovery of new compounds along with known compounds, one of which displayed potential antitubercular activity.
NATURAL PRODUCT RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Jiang Pi, Zhiyi Zhang, Enzhuo Yang, Lingming Chen, Lingchan Zeng, Yiwei Chen, Richard Wang, Dan Huang, Shuhao Fan, Wensen Lin, Hongbo Shen, Jun-Fa Xu, Gucheng Zeng, Ling Shen
Summary: Engineering Mycobacterium tuberculosis into nanoscale particles improves the safety and efficacy of the TB vaccine, providing better protection against TB infection.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Sergio Fabian Mosquera-Restrepo, Sophie Zuberogoitia, Lucie Gouxette, Emilie Layre, Martine Gilleron, Alexandre Stella, David Rengel, Odile Burlet-Schiltz, Ana Cecilia Caro, Luis F. Garcia, Cesar Segura, Carlos Alberto Pelaez Jaramillo, Mauricio Rojas, Jerome Nigou
Summary: An estimated one-third of tuberculosis (TB) cases go undiagnosed or unreported. Developing non-sputum-based point-of-care biomarker-based diagnostics for TB is a major priority. In this study, patient exhaled breath condensate (EBC) samples were analyzed to detect pulmonary TB. The presence of specific lipids, lipoglycan, and proteins in EBCs efficiently differentiated TB patients from controls. EBC analysis has the potential to facilitate clinical diagnosis of TB and monitor treatment efficacy.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Nilofer Naqvi, Rahul Srivastava, Pieu Naskar, Niti Puri
Summary: The early interactions between the BCG vaccine and host MCs play a crucial role in generating protective immune responses, but the multi-pronged effector responses of MCs on encountering BCG, such as killing, phagocytosis, and trap release, may influence the success or failure of long-term immunity provided by the BCG vaccine.
CELLULAR IMMUNOLOGY
(2021)
Article
Immunology
Margaret G. Taylor, Sarah K. Nicholas, Lisa R. Forbes Satter, Caridad Martinez, Lindsay H. Cameron
Summary: This article reports a case of an infant with inborn errors of immunity who developed infectious complications following BCG vaccination. The diagnosis of disseminated BCG infection was made using plasma metagenomic next-generation sequencing, and early antimycobacterial treatment improved the clinical outcome. The authors suggest that plasma mNGS testing should be considered as a noninvasive screen for infectious pathogens in children with IEIs before stem cell transplantation.
PEDIATRIC INFECTIOUS DISEASE JOURNAL
(2022)
Article
Microbiology
Sarah M. Batt, Szilvi Toth, Beatriz Rodriguez, Katherine A. Abrahams, Natacha Veerapen, Giacomo Chiodarelli, Liam R. Cox, Patrick J. Moynihan, Joel Lelievre, Klaus Futterer, Gurdyal S. Besra
Summary: DprE2 is an important enzyme for the synthesis of DPA and arabinogalactan, making it a significant drug target for M. tuberculosis. Two compounds from the GSK-177 box set, GSK301A and GSK032A, were identified through overexpression studies of Mt-DprE2 target. The Mt-DprE1-DprE2 complex was purified and a new in vitro DprE2 assay was developed, based on the oxidation of the reduced nicotinamide adenine dinucleotide cofactor. Although no inhibition was observed by the two GSK compounds in the DprE2 assay, spontaneous mutant generation suggested a possible pro-drug activation pathway involving fgd1 and fbiC.
Article
Biochemistry & Molecular Biology
Felicia N. N. Watson, Caroline J. Duncombe, Anya C. C. Kalata, Ethan Conrad, Sumana Chakravarty, B. Kim Lee Sim, Stephen L. L. Hoffman, Moriya J. Tsuji, Melanie J. Shears, Sean C. C. Murphy
Summary: 7DW8-5 is a potent glycolipid adjuvant that improves malaria vaccine efficacy in mice by inducing IFN-gamma and increasing protective CD8(+) T cell responses. However, there are significant differential sex-specific responses to 7DW8-5, with male mice showing lower cytokine production and reduced vaccine efficacy compared to females. These findings highlight the importance of including both female and male sexes in experimental adjuvant studies.
Review
Chemistry, Multidisciplinary
Francesca K. Lewns, Olga Tsigkou, Liam R. Cox, Ricky D. Wildman, Liam M. Grover, Gowsihan Poologasundarampillai
Summary: Advances in bioprinting have limitations in replicating the structural and biological complexity present in bone tissue. However, biomimetic approaches using hydrogels as a platform for cell signaling can enhance the biological function and development of tissue engineering models. The development of dynamic microenvironments for in vitro bone formation and remodeling is a major focus in bioprinting. Hydrogels and 3D bioprinting offer potential solutions to overcome these challenges in creating in vitro bone models.
ADVANCED MATERIALS
(2023)
Review
Chemistry, Medicinal
Saloni Yadav, Aastha Soni, Omprakash Tanwar, Rajendra Bhadane, Gurdyal S. Besra, Neha Kawathekar
Summary: This review provides an in-depth analysis of the structural requirements for DprE1 inhibitors, including both covalent and non-covalent inhibitors, their binding patterns, and their biological activity data in vitro and in vivo. It also introduces a protein quality score (PQS) and an active-site map of the DprE1 enzyme to aid in the development of new anti-TB drugs.
Article
Immunology
Daniela Correia da Silva, Peter J. Jervis, Jose A. Martins, Patricia Valentao, Paula M. T. Ferreira, David M. Pereira
Summary: Inflammation and endoplasmic reticulum stress often occur together in chronic diseases. Fisetin, a dietary flavonol, has multiple bioactivities and may be used as a pharmacological approach against ER stress and inflammation. New derivatives of fisetin were synthesized and tested, some of which are more potent inhibitors of inflammation and ER stress signaling than the parent compound.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Alexandra L. Martin, Philip N. Jemmett, Thomas Howitt, Mary H. Wood, Andrew W. Burley, Liam R. Cox, Timothy R. Dafforn, Rebecca J. L. Welbourn, Mario Campana, Maximilian W. A. Skoda, Joseph J. Thompson, Hadeel Hussain, Jonathan L. Rawle, Francesco Carla, Christopher L. Nicklin, Thomas Arnold, Sarah L. Horswell
Summary: The effect of lipid composition on models of the inner leaflet of mammalian cell membranes has been investigated. It was found that incorporating a small quantity of the anionic lipid dimyristoylphosphatidylserine (DMPS) into zwitterionic dimyristoylphosphatidylethanolamine (DMPE) bilayers resulted in significant changes in bilayer response to an applied electric field. Optimum bilayer properties were observed in the range of 10-35 mol% DMPS, which may explain the tendency for the DMPS content of cell membranes to fall within this range.
Article
Multidisciplinary Sciences
Yicheng Gong, Chuancun Wei, Jun Wang, Nengjiang Mu, Qinhong Lu, Chengyao Wu, Ning Yan, Huifang Yang, Yao Zhao, Xiuna Yang, Sudagar S. Gurcha, Natacha Veerapen, Sarah M. Batt, Zhiqiang Hao, Lintai Da, Gurdyal S. Besra, Zihe Rao, Lu Zhang
Summary: Arabinogalactan (AG) is an essential component in mycobacterial species, and AftA is a key enzyme involved in AG biosynthesis. The cryo-EM structure of Mtb AftA reveals its dimeric assembly and the participation of a metal ion in its interaction. Structural analysis and mutagenesis studies provide insights into the priming mechanism catalyzed by AftA in Mtb AG biosynthesis, which can contribute to anti-TB drug discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Nidhi Kedia-Mehta, Marta M. Pisarska, Christina Rollings, Chloe O'Neill, Conor De Barra, Cathriona Foley, Nicole A. W. Wood, Neil Wrigley-Kelly, Natacha Veerapen, Gurdyal Besra, Ronan Bergin, Nicholas Jones, Donal O'Shea, Linda V. Sinclair, Andrew E. Hogan
Summary: In this study, it was found that the activation of MAIT cells leads to increased abundance of MYC, a key metabolic regulator and transcription factor. Two MYC-controlled metabolic pathways, amino acid transport and glycolysis, were found to be necessary for MAIT cell proliferation. The study also showed that MAIT cells from obese individuals have decreased MYC abundance upon activation, resulting in impaired cell proliferation and function.
Article
Engineering, Biomedical
Amirpasha Moetazedian, Alessia Candeo, Siyun Liu, Arran Hughes, Vahid Nasrollahi, Mozafar Saadat, Andrea Bassi, Liam M. Grover, Liam R. Cox, Gowsihan Poologasundarampillai
Summary: Microfluidics have been widely used in diagnosis and screening in regenerative medicine, and now show great potential in biofabrication. However, the expensive and time-consuming lithographic processes have hindered their adoption and progress. In this study, a versatile and inexpensive manufacturing pipeline was developed to fabricate microfluidic devices with complex core-shell geometries, which matched the sizes of human arteries and arterioles. The presented 3D-printed microfluidic system is versatile, simple, and efficient, and has the potential to significantly advance the microfluidic platform in regenerative medicine.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Medicine, Research & Experimental
Suzanne E. Engelen, Francesca A. Ververs, Angela Markovska, B. Christoffer Lagerholm, Jordan M. Kraaijenhof, Laura I. E. Yousif, Yasemin-Xiomara Zurke, Can M. C. Gulersonmez, Sander Kooijman, Michael Goddard, Robert J. van Eijkeren, Peter J. Jervis, Gurdyal S. Besra, Saskia Haitjema, Folkert W. Asselbergs, Eric Kalkhoven, Hidde L. Ploegh, Marianne Boes, Vincenzo Cerundolo, G. K. Hovingh, Mariolina Salio, Edwin C. A. Stigter, Patrick C. N. Rensen, Claudia Monaco, Henk S. Schipper
Summary: This study reveals that circulating lipoproteins form complexes with lipid antigens to facilitate their transport and uptake by antigen-presenting cells, leading to enhanced iNKT cell activation. This discovery uncovers a novel mechanism of lipid antigen delivery to APCs and provides further insight into the immunological capacities of circulating lipoproteins.
Article
Biochemistry & Molecular Biology
Kriti Kalpana, Shen Yap, Moriya Tsuji, Akira Kawamura
Summary: This study reveals that Withaferin A can selectively attenuate the pro-inflammatory signaling triggered by endotoxin without impairing other immunological pathways, providing a new conceptual framework to understand the safe immune-boosting effect of Withania somnifera and possibly other medicinal plants. The findings also open new opportunities for the development of safe immunotherapeutic agents, such as vaccine adjuvants.
Article
Biochemistry & Molecular Biology
Thaiza Aline Pereira-Santos, Anderson Santos da Rocha, Agata Lopes-Ribeiro, Laura Cardoso Correa-Dias, Patricia Melo-Oliveira, Erik Vinicius de Sousa Reis, Flavio Guimaraes da Fonseca, Edel Figueiredo Barbosa-Stancioli, Moriya Tsuji, Jordana Grazziela Alves Coelho-dos-Reis
Summary: This study aimed to identify immunodominant regions of HTLV-1 Tax using peptide microarray analysis. Results showed dose-dependent reactivity of HLA-A*02:01 in all regions, with specific hotspots. In silico analysis revealed IFN-gamma-inducing peptides in the N-terminal portion and IL-4 inducers in the C-terminal portion. This research provides insight for designing immunomodulatory strategies for HTLV-1 chronic diseases.
Article
Immunology
Andrew Chancellor, Robert Alan Simmons, Rahul C. Khanolkar, Vladimir Nosi, Aisha Beshirova, Giuliano Berloffa, Rodrigo Colombo, Vijaykumar Karuppiah, Johanne M. Pentier, Vanessa Tubb, Hemza Ghadbane, Richard J. Suckling, Keith Page, Rory M. Crean, Alessandro Vacchini, Corinne De Gregorio, Verena Schaefer, Daniel Constantin, Thomas Gligoris, Angharad Lloyd, Miriam Hock, Velupillai Srikannathasan, Ross A. Robinson, Gurdyal S. Besra, Marc W. Van der Kamp, Lucia Mori, Raffaele Calogero, David K. Cole, Gennaro De Libero, Marco Lepore
Summary: Canonical MAIT TCRs with dual reactivity to microbial and self-antigens can recognize MR1 promiscuously, allowing MAIT cell responses in the absence of microbial infection. MAIT TCRs can also crossreact with self-antigens and perform T-helper-like functions in vitro. The promiscuity of MR1 recognition by a canonical MAIT TCR is associated with unique TCR β-chain features enriched in self-reactive MAIT cells of healthy individuals. These findings suggest a broader role of MAIT cells in immune homeostasis and diseases beyond microbial immunosurveillance.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Yang Xu, Tammy Ferguson, Kazuya Masuda, Mohammad Adnan Siddiqui, Kelsi Poole Smith, Olivia Vest, Brad Brooks, Ziyou Zhou, Judy Obliosca, Xiang-Peng Kong, Xunqing Jiang, Masahiro Yamashita, Tsuji Moriya, Christopher Tison
Summary: Luna Labs is developing a short carbon nanotube-based delivery platform called NanoVac, which can efficiently co-deliver mRNA and HIV-1 glycoproteins to the immune system with negligible toxicity. NanoVac stabilized the loaded mRNA and reduced the cold chain burden for vaccine deployment.
Article
Chemistry, Multidisciplinary
Alexandra L. Martin, Philip N. Jemmett, Thomas Howitt, Mary H. Wood, Andrew W. Burley, Liam R. Cox, Timothy R. Dafforn, Rebecca J. L. Welbourn, Mario Campana, Maximilian W. A. . Skoda, Joseph J. Thompson, Hadeel Hussain, Jonathan L. Rawle, Francesco Carla, Christopher L. Nicklin, Thomas Arnold, Sarah L. Horswell
Summary: The effect of lipid composition on models of mammalian cell membranes has been investigated. The presence of anionic lipid in zwitterionic lipid bilayers leads to changes in bilayer response and solvation. A specific range of anionic lipid content (10-35 mol %) provides optimal properties for bilayers, explaining the tendency for cell membranes to contain this amount of anionic lipid.