Article
Neurosciences
Yu Chen, Hui Chen, Xiao-Chen Li, Wen-Li Mi, Yu-Xia Chu, Yan-Qing Wang, Qi-Liang Mao-Ying
Summary: Toll like receptor 9 (TLR9) is a critical sensor involved in danger-associated molecular patterns (DAMPs), and its role in inflammatory pain is not well understood. This study demonstrates that downregulation of neuronal TLR9 in the spinal cord can prevent CFA-induced persistent hypersensitivity, suggesting it may be a potential treatment target for inflammatory pain.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Jun-Lin Lu, Qi-Dong Xia, Yi Sun, Yang Xun, Heng-Long Hu, Chen-Qian Liu, Jian-Xuan Sun, Jin-Zhou Xu, Jia Hu, Shao-Gang Wang
Summary: The study found that TLR4 expression is decreased in tumor tissues compared to surrounding tissues or normal tissue, and is positively correlated to the overall survival rate and cancer-specific survival rate of bladder cancer patients. Low TLR4 expression is associated with malignant performance in tumors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Maria Jose Bordagaray, Alejandra Fernandez, Jessica Astorga, Mauricio Garrido, Patricia Hernandez, Alejandra Chaparro, Maria Jesus Lira, Peter Gebicke-Haerter, Marcela Hernandez
Summary: PBMCs from individuals with AP exhibit a proinflammatory phenotype and upregulation of TLR2, associated with CpG site methylation in the promoter region of the TLR2 gene.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Zhongkun Zhang, Jimmy Chun-Tien Kuo, Siyu Yao, Chi Zhang, Hira Khan, Robert J. Lee
Summary: This article summarizes the applications and future directions of CpG ODNs in cancer immunotherapy.
Article
Audiology & Speech-Language Pathology
Chao-Hui Yang, Chung-Feng Hwang, Jiin-Haur Chuang, Wei-Shiung Lian, Feng-Sheng Wang, Ming-Yu Yang
Summary: The TLR signaling pathway plays a key role in the innate immune response to systemic infection. While systemic TLR7 agonist did not significantly affect ototoxicity, TLR9 agonist exacerbated kanamycin-induced ototoxicity and inflammation in the cochlea. This study suggests that patients with viral infections may experience more severe hearing loss when treated with aminoglycosides.
Article
Immunology
James A. Carroll, Brent Race, Katie Williams, James F. Striebel, Bruce Chesebro
Summary: The study found that adult microglia exhibited higher reactivity to exposure to LPS or IMQ, but showed decreased expression of genes when exposed to CpG-ODN 1585. In vivo experiments indicated that microglial influences on neuroinflammation were specific to the agonist, with mice with reduced microglia showing more dysregulated responses to the TLR7 agonist IMQ.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Dentistry, Oral Surgery & Medicine
Alejandra Fernandez, Jessica Astorga, Maria Jose Bordagaray, Maria Jesus Lira, Peter J. Gebicke-Haerter, Marcela Hernandez
Summary: This study explores the methylation pattern and its impact on gene transcription of the TLR9 gene in chronic periapical inflammation. The results show that demethylation of certain CpG sites in the TLR9 promoter region enhances transcriptional activity. Additionally, age and smoking were found to affect the overall methylation status of the gene.
INTERNATIONAL ENDODONTIC JOURNAL
(2022)
Review
Immunology
Niloofar Deravi, Mohadeseh Poudineh, Marzieh Pirzadeh, Hanie Yavarpour-Bali, Hoda Mehrabi, Gisou Erabi, Amene Saghazadeh, Nima Rezaei
Summary: Endothelial cells play a critical role in innate immune and inflammatory responses, and Toll-like receptors (TLRs) are key in activating innate mechanisms in ECs. Endothelial dysfunction may lead to tissue damage in various diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Critical Care Medicine
Sahil Gupta, James N. Tsoporis, Song-Hui Jia, Claudia C. dos Santos, Thomas G. Parker, John C. Marshall
Summary: This article discusses how host cells recognize danger signals using pattern recognition receptors, focusing on Toll-like receptors (TLRs) as the most studied class of PRRs. It reviews the expression, regulation, and function of different TLRs, emphasizing TLR-4, and how TLR adaptor protein binding directs intracellular signaling to activate or terminate an innate immune response. The recent progress in research on the involvement of S100 proteins as ligands for TLR-4 in inflammatory disease is also highlighted.
Article
Biochemistry & Molecular Biology
Zeshi Li, Ronald Derking, Wen-Hsin Lee, Gerlof P. Bosman, Andrew B. Ward, Rogier W. Sanders, Geert-Jan Boons
Summary: A one-step enzymatic conjugation approach was developed to covalently attach small molecule adjuvants to viral glycoproteins without compromising epitope integrity. This method allows efficient immune activation and has been successfully used to modify a native-like HIV envelope trimer with a Toll-like receptor 7/8 agonist.
Article
Immunology
Rohit Kumar Tiwari, Pragya Chandrakar, Chhedi Lal Gupta, Uzma Sayyed, Rafia Shekh, Preeti Bajpai
Summary: The study demonstrated the adjuvant properties of a novel CpG sequence found in the Leishmania donovani genome to enhance immune response. By combining parasite antigens with adjuvants and nanoparticle carriers, a significant cellular and humoral immune response was generated, reducing parasitic load in the liver, spleen, and bone marrow.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Immunology
Kai Yao, Zheng Wang, Cheng Peng, Yong Wang, Bichen Xue, Yulin Tang, Zhichao Wang, Hongbo Xu
Summary: This study aims to determine whether SQV is an HMGB1-specific and MyD88-dependent TLR4 signaling inhibitor and which precise signaling element of TLR4 is targeted by SQV. The findings showed that SQV suppresses MyD88- and TRIF-dependent pathways, downregulates NF-κB and IRF3, and decreases the dimerization of TLR4 following LPS or HMGB1 stimulation.
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Malgorzata Sobstyl, Paulina Niedzwiedzka-Rystwej, Rafal Hrynkiewicz, Dominika Bebnowska, Izabela Korona-Glowniak, Marcin Pasiarski, Barbara Sosnowska-Pasiarska, Jolanta Smok-Kalwat, Stanislaw Gozdz, Anna Sobstyl, Wojciech Polkowski, Jacek Rolinski, Ewelina Grywalska
Summary: The study demonstrated the significance of TLR2 as a biomarker in advanced stage ovarian cancer by showing significantly higher expression levels in women with more advanced OC. This research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and increasing survival in confirmed ovarian cancer patients.
Review
Biochemistry & Molecular Biology
Saahithh Redddi Patlola, Gary Donohoe, Declan P. McKernan
Summary: Toll-like receptors (TLRs) are pattern recognition receptors that protect the brain from self and foreign antigens/pathogens and can elicit a harmful or beneficial immune response. TLR activation has been associated with neurodegenerative diseases and cytokine imbalance in schizophrenia. This review explores the current literature on TLRs, their potential role in schizophrenia pathogenesis, factors affecting TLR activity and their impact on cognitive performance in schizophrenia.
Article
Biochemistry & Molecular Biology
Miriam Meloni, Ilenia Sana, Maria Elena Mantione, Michela Riba, Marta Muzio
Summary: This study analyzed the expression profiles of different leukemia cell lines before and after CpG stimulation. The results identified NFKBIZ mRNA and IkBz protein as robust markers of TLR9 activation in MEC2 and PCL12 cell lines, but not in HG3 cells. Comparison with patient samples indicated that MEC2 more closely resembled patient cells in terms of TLR responsiveness, with high levels of IkBz expression and fewer regulated genes.
Article
Immunology
Jillian S. Y. Lau, Deborah Cromer, Mykola Pinkevych, Sharon R. Lewin, Thomas A. Rasmussen, James H. McMahon, Miles P. Davenport
Summary: This study used mathematical models to explore ways to improve ATI study design to maximize statistical power and minimize risks to participants.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
Arya SheelaNair, Aleksandra S. Romanczuk, Rosemary A. Aogo, Rohit Nemai Haldar, Lianne I. M. Lansink, Deborah Cromer, Yandira G. Salinas, R. Kiplin Guy, James S. McCarthy, Miles P. Davenport, Ashraful Haque, David S. Khoury
Summary: This study compared the effects of different anti-malarial drugs on mice infected with malaria. The results showed that different drugs varied in their ability to reduce parasite count and had different mechanisms of action. This suggests that although the parasite clearance curves may be similar, the drugs have different capacities to inhibit, kill, and clear parasites.
Article
Multidisciplinary Sciences
Sandile Cele, Laurelle Jackson, David S. Khoury, Khadija Khan, Thandeka Moyo-Gwete, Houriiyah Tegally, James Emmanuel San, Deborah Cromer, Cathrine Scheepers, Daniel G. Amoako, Farina Karim, Mallory Bernstein, Gila Lustig, Derseree Archary, Muneerah Smith, Yashica Ganga, Zesuliwe Jule, Kajal Reedoy, Shi-Hsia Hwa, Jennifer Giandhari, Jonathan M. Blackburn, Bernadett Gosnell, Salim S. Abdool Karim, Willem Hanekom, Anne von Gottberg, Jinal N. Bhiman, Richard J. Lessells, Mahomed-Yunus S. Moosa, Miles P. Davenport, Tulio de Oliveira, Penny L. Moore, Alex Sigal
Summary: The study found that the Omicron variant has reduced neutralizing effectiveness in individuals vaccinated with Pfizer BNT162b2, but those who had previously been infected with SARS-CoV-2 showed better neutralization against Omicron.
Article
Biochemistry & Molecular Biology
Sharon L. Wong, Nikhil T. Awatade, Miro A. Astore, Katelin M. Allan, Michael J. Carnell, Iveta Slapetova, Po-Chia Chen, Jeffry Setiadi, Elvis Pandzic, Laura K. Fawcett, John R. Widger, Renee M. Whan, Renate Griffith, Chee Y. Ooi, Serdar Kuyucak, Adam Jaffe, Shafagh A. Waters
Summary: This study investigated the structural and functional defects of the rare CFTR mutation R352Q in cell models of the airway and gut. The mutation showed residual CFTR function, which could be restored by CFTR potentiators but not the corrector. Molecular dynamics simulations indicated a chloride conductance defect rather than a gating defect. The combination of in vitro patient-derived cell models and in silico simulations can improve predictions of modulator response and aid in CF precision medicine.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Immunology
Kathleen M. Wragg, Wen Shi Lee, Marios Koutsakos, Hyon-Xhi Tan, Thakshila Amarasena, Arnold Reynaldi, Grace Gare, Penny Konstandopoulos, Kirsty R. Field, Robyn Esterbauer, Helen E. Kent, Miles P. Davenport, Adam K. Wheatley, Stephen J. Kent, Jennifer A. Juno
Summary: Wragg and colleagues tracked clonal populations of spike-specific CD4(+) cT(FH) cells using MHC class II tetramers and TCR beta sequencing in convalescent individuals with COVID-19 or SARS-CoV-2-vaccinated individuals. They found that both infection and vaccination induced CD4(+) T cell responses to the spike protein and that these responses correlated with neutralizing antibodies. Secondary exposure led to the recall of CD4(+) T cells with a transitory CXCR3(+) phenotype and expansion of cT(FH) cells temporarily expressing ICOS, CD38, and PD-1. The study demonstrates that stable pools of cT(FH) and memory CD4(+) T cells established by infection and/or vaccination can be efficiently recalled and may contribute to long-term protection against SARS-CoV-2.
Editorial Material
Cell Biology
Hyon-Xhi Tan, Miles P. Davenport, Stephen J. Kent, Adam K. Wheatley
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Health Care Sciences & Services
Sharon L. Wong, Elvis Pandzic, Egi Kardia, Katelin M. Allan, Renee M. Whan, Shafagh A. Waters
Summary: Infection control and antibiotic therapy are crucial for managing airway infections in patients with cystic fibrosis. The use of airway epithelial cell cultures grown at air-liquid interface (ALI) provides a physiologically relevant model for studying respiratory infections. Immunofluorescence staining and imaging are effective tools for understanding host-pathogen interactions and exploring potential treatments. A quantitative fluorescence microscopy assay using a graphical user interface (GUI) package is described for identifying specific cell populations and pathogen targets in ALI cultures.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Multidisciplinary Sciences
Cybelle Tabilas, David S. Iu, Ciaran W. P. Daly, Kristel J. Yee Mon, Arnold Reynaldi, Samantha P. Wesnak, Jennifer K. Grenier, Miles P. Davenport, Norah L. Smith, Andrew Grimson, Brian D. Rudd
Summary: Microbial exposure during development can have long-lasting effects on an individual's health, but how early microbial exposure leads to permanent changes in the immune system is still unclear. This study shows that early microbial exposure results in the preferential expansion of specific CD8+ T cell populations, which persist and provide enhanced immune protection against intracellular pathogens. Interestingly, this microbial education occurs during thymic development and involves changes in epigenetic programming.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pediatrics
Katelin M. Allan, Miro A. Astore, Laura K. Fawcett, Sharon L. Wong, Po-Chia Chen, Renate Griffith, Adam Jaffe, Serdar Kuyucak, Shafagh A. Waters
Summary: Cystic Fibrosis (CF) is caused by mutations in the CFTR gene, and targeted therapies have been developed to restore the function of CFTR protein. This study demonstrated in vitro and in vivo that a combination of modulators can effectively address the folding and gating defects of CFTR.
FRONTIERS IN PEDIATRICS
(2022)
Article
Multidisciplinary Sciences
Firoz Anwar, Turky Omar Asar, Fahad A. Al-Abassi, Vikas Kumar, Sultan Alhayyani
Summary: This study investigates the effect of a diet mixed with sea and table salts on cardiac remodeling and finds that the addition of natural sea salt has a significant beneficial effect on cardiac dysfunction.
JOURNAL OF TAIBAH UNIVERSITY FOR SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Sharon L. Wong, Egi Kardia, Abhishek Vijayan, Bala Umashankar, Elvis Pandzic, Ling Zhong, Adam Jaffe, Shafagh A. Waters
Summary: Localized and chronic hypoxia affects the function and structure of airway stem cells and differentiated epithelium in individuals with cystic fibrosis (CF). The study investigated the impact of chronic hypoxia on nasal epithelial cells (hNECs) derived from CF and non-CF individuals. The results showed that chronic hypoxia led to alterations in morphology, global proteomics, and function of hNECs, including reduced barrier integrity and modulation of cilia motility and ion transport. The activity of epithelial sodium and CFTR ion channels was reduced under chronic hypoxia, affecting the response to CFTR-targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
David S. Khoury, Steffen S. Docken, Kanta Subbarao, Stephen J. Kent, Miles P. Davenport, Deborah Cromer
Summary: Booster vaccination is necessary to combat waning immunity and variants of SARS-CoV-2. Data on neutralization titers from multiple sources suggest that using ancestral vaccines can enhance protection against symptomatic and severe disease caused by variant viruses. Variant-modified vaccines may provide additional benefits. This study provides evidence-based guidance for future COVID-19 vaccine regimens.
Article
Multidisciplinary Sciences
Thomas G. Molley, Shouyuan Jiang, Louis Ong, Chantal Kopecky, Chavinya D. Ranaweera, Gagan K. Jalandhra, Laura Milton, Egi Kardia, Zeheng Zhou, Jelena Rnjak-Kovacina, Shafagh A. Waters, Yi-Chin Toh, Kristopher A. Kilian Abh
Summary: This work developed a high-loading enzyme encapsulation approach that precisely controls the oxygen content in cell culture, demonstrating its application in various cells and promoting neovascularization. This platform's simplicity and flexibility make it useful for studying oxygen-mediated processes in any in vitro or in vivo format.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Deborah Cromer, Megan Steain, Arnold Reynaldi, Timothy E. Schlub, Shanchita R. Khan, Sarah C. Sasson, Stephen J. Kent, David S. Khoury, Miles P. Davenport
Summary: The study demonstrates a strong correlation between neutralising antibody titres and vaccine effectiveness against symptomatic and severe COVID-19. Predicted neutralising antibody titres are strongly correlated with observed vaccine effectiveness, and the loss of neutralising antibodies over time and to new variants is predictive of observed vaccine protection against severe COVID-19.
NATURE COMMUNICATIONS
(2023)
Article
Health Care Sciences & Services
Laura K. Fawcett, Nihan Turgutoglu, Katelin M. Allan, Yvonne Belessis, John Widger, Adam Jaffe, Shafagh A. Waters
Summary: Primary nasal epithelial cells and culture models are essential tools for diagnosing, researching and developing drugs for airway diseases. This study compared two cytology brushes, Olympus and Endoscan, in collecting nasal epithelial cells. Results showed that the choice of brush did not affect diagnostic accuracy, but the Endoscan brush was more efficient in collecting total and live cells. Furthermore, the Endoscan brush was more cost-effective compared to the Olympus brush.
JOURNAL OF PERSONALIZED MEDICINE
(2023)