Article
Biochemical Research Methods
Yongjun Choi, Vijaya Sunkara, Yeojin Lee, Yoon-Kyoung Cho
Summary: Dendritic cells (DCs) play essential roles in immune responses, with exhausted matured DCs (xmDCs) showing significantly different cellular migration behavior compared to active matured DCs (amDCs) and immature DCs (iDCs). Although xmDCs exhibit slower, less persistent, and less diffusive random motility, their CCR7-dependent chemotactic motility remains well-preserved.
Article
Biochemistry & Molecular Biology
Sandra Gunne, Marie Schwerdtner, Marina Henke, Ann-Kathrin Schneider, Lucas Keutmann, Eva Boettcher-Friebertshaeuser, Susanne Schiffmann
Summary: The study found that TMPRSS2 has an impact on the activation of toll-like receptors in dendritic cells and cytokine release, but has minimal effect on chemokine receptors. TMPRSS2 seems to suppress cytokine release in cDCs, while possibly mediating cytokine release in pDCs, depending on the activated TLR.
Article
Immunology
Patrice A. Mawa, Mateusz Hasso-Agopsowicz, Lawrence Lubyayi, Grace Nabakooza, Marjorie Nakibuule, Rose Blitz, Li Dun, Abha Govind, Pontiano Kaleebu, Emily L. Webb, Alison M. Elliott, Hazel M. Dockrell, Stephen Cose, Steven G. Smith
Summary: BCG vaccination induces similar immune responses to PPD but different responses to ESAT6/CFP10 in infants from Uganda and the UK. Maternal LTBI and infant exposure or infection with mycobacteria do not impact the immune response to BCG. Global differences in immune response to BCG are likely due to other factors.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Sizhu Amelia Chen, Elena Arutyunova, Jimmy Lu, Muhammad Bashir Khan, Wioletta Rut, Mikolaj Zmudzinski, Shima Shahbaz, Jegan Iyyathurai, Eman W. Moussa, Zoe Turner, Bing Bai, Tess Lamer, James A. Nieman, John C. Vederas, Olivier Julien, Marcin Drag, Shokrollah Elahi, Howard S. Young, M. Joanne Lemieux
Summary: The main protease of SARS-CoV-2 (Mpro) plays a crucial role in virus replication and is considered a promising drug target. This study examined the impact of mutations in Mpro on its function and substrate specificity. The results revealed changes in substrate binding, viral peptide cleavage, and alterations in the proteolysis of host proteins involved in antiviral mechanisms. However, the potency of two antiviral drugs, nirmatrelvir (Pfizer) and AVI-8053, remained unaffected by these mutations, suggesting that Mpro remains a viable drug candidate as the virus evolves.
ACS CENTRAL SCIENCE
(2023)
Article
Geriatrics & Gerontology
Jan Spaas, Richie P. Goulding, Charly Keytsman, Lena Fonteyn, Jack van Horssen, Richard T. Jaspers, Bert O. Eijnde, Rob C. I. Wust
Summary: Patients with multiple sclerosis (MS) have lower exercise tolerance due to reduced skeletal muscle oxidative phenotype. However, skeletal muscle mitochondria seem resistant to the effects of exercise training, suggesting that other physiological systems may be driving the improvements in exercise capacity following exercise training in MS.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Dermatology
J. Sulaimani, D. Cluxton, J. Clowry, A. Petrasca, O. E. Molloy, B. Moran, C. M. Sweeney, A. Malara, N. McNicholas, C. McGuigan, B. Kirby, J. M. Fletcher
Summary: DMF has been shown to increase the frequency of Treg cells and decrease Th17 cells in patients with psoriasis. It also inhibits T cell activation and proliferation in response to stimulation, while enhancing the resistance of Treg cells to oxidative stress induced by DMF.
BRITISH JOURNAL OF DERMATOLOGY
(2021)
Article
Infectious Diseases
Brenda Rocamonde, Nicolas Futsch, Noemia Orii, Omran Allatif, Augusto Cesar Penalva de Oliveira, Renaud Mahieux, Jorge Casseb, Helene Dutartre
Summary: The study found that innate immune cell responsiveness is lower in HAM/TSP patients compared to asymptomatic carriers, but they are more sensitive to inflammatory responses. This sustained inflammatory responsiveness could be linked to or be at the origin of the neuroinflammatory status in HAM/TSP patients.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Immunology
Guillermo Arango Duque, Renaud Dion, Christine Matte, Aymeric Fabie, Julien Descoteaux, Simona Staeger, Albert Descoteaux
Summary: This study revealed a novel function for the ERGIC/Golgi resident SNARE Sec22b in regulating the production and release of inflammatory mediators, involving the control of cytokine release and NO synthesis. Pharmacological blockade of the secretory pathway or RNA interference of Sec22b can affect these processes, indicating a key role of this SNARE protein.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Hematology
Lara Kristina Klauer, Olga Schutti, Selda Ugur, Fatemeh Doraneh-Gard, Daniel Christoph Amberger, Nicole Rogers, Doris Kramer, Andreas Rank, Christoph Schmid, Britta Eiz-Vesper, Helga Maria Schmetzer
Summary: The study demonstrates the potential of leukaemia-derived dendritic cells (DCleu) to activate immune responses and enhance leukaemia-specific immune reactions. Evaluating immune responses mediated by DC/DCleu through IFNy secretion proves to be an effective way to monitor the efficacy of leukaemia immunotherapy.
TRANSFUSION MEDICINE AND HEMOTHERAPY
(2022)
Review
Immunology
Antoine Roquilly, Justine D. Mintern, Jose A. Villadangos
Summary: Macrophages and conventional dendritic cells are crucial for maintaining tissue homeostasis, coordinating immune responses, and fighting against infections and cancer. They acquire spatiotemporal adaptations in response to different environmental challenges, but these adaptations can also lead to immunosuppression. Understanding their development and adaptation mechanisms can help harness their beneficial outcomes and minimize their adverse effects.
ANNUAL REVIEW OF IMMUNOLOGY
(2022)
Article
Oncology
Tony Yao, Patrick T. Rudak, Celine M. Laumont, Alex R. Michaud, Rasheduzzaman Rashu, Natasha N. Knier, Paula J. Foster, Hamish E. G. McWilliam, Jose A. Villadangos, Brad H. Nelson, Gabriel E. DiMattia, Trevor G. Shepherd, S. M. Mansour Haeryfar
Summary: Research on mucosa-associated invariant T (MAIT) cells in epithelial ovarian cancer (EOC) reveals their low frequency in tumors but potential immunomodulatory and cytotoxic properties. In a mouse model, MAIT cells showed IL-17A and IFN-gamma production in the peritoneal cavity but lost these functions with tumor progression. Ascitic MAIT cells in EOC patients exhibit inducible effector functions, suggesting potential modifications for future immunotherapeutic strategies.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Cell Biology
Rebecca Seneviratna, Samuel J. Redmond, Hamish E. G. McWilliam, Rangsima Reantragoon, Jose A. Villadangos, James McCluskey, Dale Godfrey, Nicholas A. Gherardin
Summary: Recent studies have shown that MR1-restricted T cells can react to a variety of antigens, including tumor cells and tumor-derived self-antigens. By using TCR gene transfer and engineered MR1-expressing antigen-presenting cells, researchers further investigated the reactivity of MR1-restricted TCRs and found differential dependence on MR1 position and competitive inhibition by ligands. However, TCR-expressing reporter cell lines failed to fully replicate the previously reported tumor specificity, suggesting the importance of accessory molecules in MR1-dependent tumor reactivity.
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Immunology
Shivam K. Purohit, Carolyn Samer, Hamish E. G. McWilliam, Renee Traves, Megan Steain, Brian P. McSharry, Paul R. Kinchington, David C. Tscharke, Jose A. Villadangos, Jamie Rossjohn, Allison Abendroth, Barry Slobedman
Summary: This study demonstrates that varicella zoster virus suppresses the expression of antigen presentation molecule MR1, highlighting the intricate temporal relationship between infection and ligand availability. The study also suggests that VZV likely encodes multiple viral genes targeting MR1.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Patrick Schriek, Alan C. Ching, Nagaraj S. Moily, Jessica Moffat, Lynette Beattie, Thiago M. Steiner, Laine M. Hosking, Joshua M. Thurman, V. Michael Holers, Satoshi Ishido, Mireille H. Lahoud, Irina Caminschi, William R. Heath, Justine D. Mintern, Jose A. Villadangos
Summary: Marginal zone B cells acquire dendritic cell-like properties through the trogocytic acquisition of MHC II-C3 complexes from conventional dendritic cells.
Article
Critical Care Medicine
Tanguy Chaumette, Raphael Cinotti, Alice Molle, Pierre Solomon, Louise Castain, Cynthia Fourgeux, Hamish E. G. McWilliam, Barbara Misme-Aucouturier, Alexis Broquet, Cedric Jacqueline, Mickael Vourc'h, Delphine Fradin, Celine Bossard, Laurent David, Emmanuel Montassier, Cecile Braudeau, Regis Josien, Jose A. Villadangos, Karim Asehnoune, Celine Bressollette-Bodin, Jeremie Poschmann, Antoine Roquilly
Summary: Brain injury induces immunosuppression, increasing the risk of viral reactivations and impairing neurological recovery. This study found that lung replication of herpesviridae is associated with poor recovery after brain injury, and a specific monocyte signature can predict the neurological outcome at 6 months.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Biochemical Research Methods
Vanta J. Jameson, Tina Luke, Yuting Yan, Angela Hind, Maximilien Evrard, Kevin Man, Laura K. Mackay, Axel Kallies, Jose A. Villadangos, Hamish E. G. McWilliam, Alexis Perez-Gonzalez
Summary: Understanding the impact of autofluorescence on signal resolution in cytometry is crucial for experimental design and data quality. This study provides mathematical predictions and empirical evidence to support the importance of autofluorescence extraction through full spectrum unmixing. The study also presents a novel method for isolating pure cell subset-specific autofluorescence profiles based on high dimensionality reduction algorithms.
Article
Multidisciplinary Sciences
Haiyin Liu, Kayla R. Wilson, Ashley M. Firth, Christophe Macri, Patrick Schriek, Annabelle B. Blum, Javiera Villar, Samuel Wormald, Mitch Shambrook, Bangyan Xu, Hui Jing Lim, Hamish E. G. McWilliam, Andrew F. Hill, Laura E. Edgington-Mitchell, Irina Caminschi, Mireille H. Lahoud, Elodie Segura, Marco J. Herold, Jose A. Villadangos, Justine D. Mintern
Summary: This study reveals the critical role of ubiquitin-like protein 3 (UBL3) in the trafficking process controlled by MARCH1. UBL3 has wide-ranging immunological consequences and is essential for immune responses.
NATURE COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Mickael Vourc'h, Antoine Roquilly, Adrien Foucher, Christelle Retiere, Fanny Feuillet, Sapna Devi, Hamish E. G. McWilliam, Cecile Braudeau, Geraldine Bourreille, Abderrahman Hachani, Dermot O'Kane, Scott N. Mueller, Joseph Ischia, Jean-Christian Roussel, Jean-Christophe Rigal, Regis Josien, Bertrand Rozec, Jose A. Villadangos, Karim Asehnoune
Summary: This study found that transfusion of packed red blood cells with high levels of MRP_14 may increase the incidence of AKI after cardiac surgery. Higher concentrations of MRP_14 were found in packed red blood cells from female donors or prepared by whole blood filtration.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2022)
Article
Cell Biology
Marine Gros, Elodie Segura, Derek C. Rookhuizen, Blandine Baudon, Sandrine Heurtebise-Chretien, Nina Burgdorf, Mathieu Maurin, Eugene A. Kapp, Richard J. Simpson, Patrycja Kozik, Jose A. Villadangos, Mathieu J. M. Bertrand, Marianne Burbage, Sebastian Amigorena
Summary: Despite its importance in immune responses, the molecular pathways underlying antigen cross-presentation are not fully understood. This study reveals that membrane repair plays a crucial role in containing antigen export to the cytosol and cross-presentation in conventional dendritic cells (cDCs).
Article
Cell Biology
Hui Jing Lim, Jacinta M. Wubben, Cristian Pinero Garcia, Sebastian Cruz-Gomez, Jieru Deng, Jeffrey Y. W. Mak, Abderrahman Hachani, Regan J. Anderson, Gavin F. Painter, Jesse Goyette, Shanika L. Amarasinghe, Matthew E. Ritchie, Antoine Roquilly, David P. Fairlie, Katharina Gaus, Jamie Rossjohn, Jose A. Villadangos, Hamish E. G. McWilliam
Summary: MR1 is a conserved microbial immune-detection system in mammals that presents antigens to specific lymphocytes, contributing to host defense and tissue repair. This study reveals that human MR1 interacts with the endocytic adaptor protein 2 (AP2) complex to regulate its internalization from the cell surface, thus controlling antigen presentation and microbial metabolic detection.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Viacheslav Kriachkov, Angelique R. Ormsby, Eric P. Kusnadi, Hamish E. G. McWilliam, Justine D. Mintern, Shanika L. Amarasinghe, Matthew E. Ritchie, Luc Furic, Danny M. Hatters
Summary: Hexanucleotide expansion mutations in C9ORF72 are a common cause of amyotrophic lateral sclerosis. Our study explores the molecular features of translation stalling induced by arginine-rich dipeptide repeats (DPRs) and investigates whether ribosome quality control (RQC) mechanisms regulate translation elongation on sequences encoding DPRs. We found that DPRs lead to stalling in a length-dependent manner and that charged amino acids, such as arginine, lysine, glutamic acid, or aspartic acid, in the DPRs contribute to more pronounced stalling. Furthermore, our findings suggest limited natural regulatory responses to resolve the arginine-rich DPR stalls.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Immunology
Zahra Elahi, Paul W. Angel, Suzanne K. Butcher, Nadia Rajab, Jarny Choi, Yidi Deng, Justine D. Mintern, Kristen Radford, Christine A. Wells
Summary: Dendritic cells (DCs) are functionally diverse and play important roles in human tissues. However, limited numbers and short lifespan of DCs in circulation have hindered the understanding of human DC biology. In this study, a transcriptional atlas of human DCs was constructed by combining samples from multiple expression profiling studies. The study revealed significant gene expression variation of DC subset-defining markers across different tissues and upon viral or bacterial stimulation. The study also highlighted the differences between in vitro-derived DC subsets and their in vivo counterparts, and provided evidence that in vitro-differentiated DCs fail to capture the repertoire of primary DC subsets or behaviors. The construction of the reference DC atlas provides a valuable resource for identifying and annotating tissue-specific DC subsets from single-cell datasets, as well as benchmarking new in vitro models of DC biology.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Caroline L. Ashley, Brian P. McSharry, Hamish E. G. McWilliam, Richard J. Stanton, Ceri A. Fielding, Rommel A. Mathias, David P. Fairlie, James McCluskey, Jose A. Villadangos, Jamie Rossjohn, Allison Abendroth, Barry Slobedman
Summary: This study reveals that human cytomegalovirus (HCMV) inhibits the MR1 pathway and disrupts the MR1:MAIT cell axis through the viral protein gpUS9. The interaction between this virus and MAIT cells in the context of viral infection is not well characterized.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Patrick Schriek, Jose A. Villadangos
Summary: Antigen-presenting cells capture or synthesize antigens and present them on their plasma membrane through major histocompatibility complex (MHC) molecules. Trogocytosis is a mechanism where cells acquire fragments from other cells and incorporate them into their own plasma membrane, including intact antigens and MHC molecules. Trogocytosis expands cellular immunological functions with both beneficial and deleterious consequences.
CURRENT OPINION IN IMMUNOLOGY
(2023)